Cell Transplantation 24(9) Abstracts

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Cell Transplantation, Vol. 24, pp. 1661-1678, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X683485
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

Mesenchymal Stem Cells for Treating Articular Cartilage Defects and Osteoarthritis

Yu Wang, Mei Yuan, Quan-yi Guo, Shi-bi Lu, and Jiang Peng

Institute of Orthopedics, Chinese PLA General Hospital, Beijing, China

Articular cartilage damage and osteoarthritis are the most common joint diseases. Joints are prone to damage caused by sports injuries or aging, and such damage regularly progresses to more serious joint disorders, including osteoarthritis, which is a degenerative disease characterized by the thinning and eventual wearing out of articular cartilage, ultimately leading to joint destruction. Osteoarthritis affects millions of people worldwide. Current approaches to repair of articular cartilage damage includemosaicplastymicrofracture, and injection of autologous chondrocytes. These treatments relieve pain and improve joint function, but the long-term results are unsatisfactory. The long-term success of cartilage repair depends on development of regenerative methodologies that restore articular cartilage to a near-native state. Two promising approaches are (i) implantation of engineered constructs of mesenchymal stem cell (MSC)-seeded scaffolds, and (ii) delivery of an appropriate population of MSCs by direct intra-articular injection. MSCs may be used as trophic producers of bioactive factors initiating regenerative activities in a defective joint. Current challenges in MSC therapy are the need to overcome current limitations in cartilage cell purity and to in vitro engineer tissue structures exhibiting the required biomechanical properties. This review outlines the current status of MSCs used in cartilage tissue engineering and in cell therapy seeking to repair articular cartilage defects and related problems. MSC-based technologies show promise when used to repair cartilage defects in joints.

Key words: Articular cartilage; Mesenchymal stem cells (MSCs); Tissue engineering; Osteoarthritis

Received July 7, 2013; final acceptance July 24, 2014. Online prepub date: July 25, 2014.
Address correspondence to Jiang Peng, Institute of Orthopedics, Chinese PLA General Hospital, FuXing Road 28#, HaiDian District, 100853 Beijing, China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1679-1686, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X685050
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Review

Cell-Based Therapies in Lower Urinary Tract Disorders

Chaitanya Gopinath,* Peter Ponsaerts,† and Jean Jacques Wyndaele*

*Department of Urology, University of Antwerp, Antwerp, Belgium
†Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Antwerp, Belgium

Cell-based therapy for the bladder has its beginnings in the 1990s with the successful isolation and culture of bladder smooth muscle cells. Since then, several attempts have been made to artificially implant native cell types and stem cell-derived cells into damaged bladders in the form of single-cell injectables or as grafts seeded onto artificial extracellular matrix. We critically examined in the literature the types of cells and their probable role as an alternative to non-drug-based, non-bowel-based graft replacement therapy in disorders of the urinary bladder. The limitations and plausible improvements to these novel therapies have also been discussed, keeping in mind an ideal therapy that could suit most bladder abnormalities arising out of varied number of disorders. In conclusion, muscle-derived cell types have consistently proven to be a promising therapy to emerge in the coming decade. However, tissue-engineered constructs have yet to prove their success in preclinical and long-term clinical setting.

Key words: Cell transplantation; Bladder; Literature review; Tissue engineering; Urology

Received February 19, 2014; final acceptance September 09, 2014. Online prepub date: October 06, 2014.
Address correspondence to Prof. Dr. Jean-Jacques Wyndaele, Department of Urology, University of Antwerp and University Hospital Antwerp, Wilrijkstraat 10, B-2650, Edegem, Antwerp, Belgium. Tel: + 32 3 821 3511; Fax: + 32 3 821 4479; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it



Cell Transplantation, Vol. 24, pp. 1687-1698, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X684619
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Mesenchymal Stromal Cells Improve Renovascular Function in Polycystic Kidney Disease

Federico Franchi,* Karen M. Peterson,* Rende Xu,* Brent Miller,* Peter J. Psaltis,*† Peter C. Harris,‡ Lilach O. Lerman,‡ and Martin Rodriguez-Porcel*

*Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
†Department of Medicine, University of Adelaide, Adelaide, Australia
‡Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

Polycystic kidney disease (PKD) is a common cause of end-stage renal failure, for which there is no accepted treatment. Progenitor and stem cells have been shown to restore renal function in a model of renovascular disease, a disease that shares many features with PKD. The objective of this study was to examine the potential of adult stem cells to restore renal structure and function in PKD. Bone marrow-derived mesenchymal stromal cells (MSCs, 2.5 × 105) were intrarenally infused in 6-week-old PCK rats. At 10 weeks of age, PCK rats had an increase in systolic blood pressure (SBP) versus controls (126.22 ± 2.74 vs. 116.45 ± 3.53 mmHg, p < 0.05) and decreased creatinine clearance (3.76 ± 0.31 vs. 6.10 ± 0.48 μl/min/g, p < 0.01), which were improved in PKD animals that received MSCs (SBP: 114.67 ± 1.34 mmHg, and creatinine clearance: 4.82 ± 0.24 μl/min/g, p = 0.001 and p = 0.003 vs. PKD, respectively). MSCs preserved vascular density and glomeruli diameter, measured using microcomputed tomography. PCK animals had increased urine osmolality (843.9 ± 54.95 vs. 605.6 ± 45.34 mOsmp < 0.01 vs. control), which was improved after MSC infusion and not different from control (723.75 ± 56.6 mOsmp = 0.13 vs. control). Furthermore, MSCs reduced fibrosis and preserved the expression of proangiogenic molecules, while cyst size and number were unaltered by MSCs. Delivery of exogenous MSCs improved vascular density and renal function in PCK animals, and the benefit was observed up to 4 weeks after a single infusion. Cell-based therapy constitutes a novel approach in PKD.

Key words: Polycystic kidney disease (PKD); Mesenchymal stromal cells (MSCs); Vasculature; Renal function; Kidney

Received May 21, 2014; final acceptance September 4, 2014. Online prepub date: October 6, 2014.
Address corresponding to Martin Rodriguez-Porcel, M.D., 200 First St. SW, Rochester, MN 55905, USA. Tel: +1-507-284-4442; Fax: +1-507-266-0228; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1699-1715, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X685087
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Mesenchymal Stem Cells Overexpressing Angiotensin-Converting Enzyme 2 Rescue Lipopolysaccharide-Induced Lung Injury

Hongli He,1 Ling Liu,1 Qihong Chen, Airan Liu, Shixia Cai, Yi Yang, Xiaomin Lu, and Haibo Qiu

Department of Critical Care Medicine, Zhongda Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, P. R. China

Bone marrow-derived mesenchymal stem cells (MSCs), which have beneficial effects in acute lung injury (ALI), can serve as a vehicle for gene therapy. Angiotensin-converting enzyme 2 (ACE2), a counterregulatory enzyme of ACE that degrades angiotensin (Ang) II into Ang 1–7, has a protective role against ALI. Because ACE2 expression is severely reduced in the injured lung, a therapy targeted to improve ACE2 expression in lung might attenuate ALI. We hypothesized that MSCs overexpressing ACE2 would have further benefits in lipopolysaccharide (LPS)-induced ALI mice, when compared with MSCs alone. MSCs were transduced with ACE2 gene (MSC-ACE2) by a lentiviral vector and then infused into wild-type (WT) and ACE2 knockout (ACE2−/y) mice following an LPS-induced intratracheal lung injury. The results demonstrated that the lung injury of ALI mice was alleviated at 24 and 72 h after MSC-ACE2 transplantation. MSC-ACE2 improved the lung histopathology and had additional anti-inflammatory effects when compared with MSCs alone in both WT and ACE2−/y
ALI mice. MSC-ACE2 administration also reduced pulmonary vascular permeability, improved endothelial barrier integrity, and normalized lung eNOS expression relative to the MSC group. The beneficial effects of MSC-ACE2 could be attributed to its recruitment into the injured lung and enhanced local expression of ACE2 protein without changing the serum ACE2 levels after MSC-ACE2 transplantation. The biological activity of the increased ACE2 protein decreased the Ang II amount and increased the Ang 1–7 level in the lung when compared with the ALI and MSC-only groups, thereby inhibiting the detrimental effects of accumulating Ang II. Therefore, compared to MSCs alone, the administration of MSCs overexpressing ACE2 resulted in a further improvement in the inflammatory response and pulmonary endothelial function of LPS-induced ALI mice. These additional benefits could be due to the degradation of Ang II that accompanies the targeted overexpression of ACE2 in the lung.

Key words: Mesenchymal stem cells (MSCs); Angiotensin-converting enzyme 2 (ACE2); Acute lung injury (ALI); Gene therapy

Received January 16, 2014; final acceptance September 20, 2014. Online prepub date: October 6, 2014.
1These authors provided equal contribution to this work.
Address correspondence to Haibo Qiu, Department of Critical Care Medicine, Zhongda Hospital, Southeast University School of Medicine, No. 87 Ding Jiaqiao, Nanjing (210009), Jiangsu, P. R. China. Tel: +86-25-83262551; Fax: +86-25-83272123; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1717-1731, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X684592
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Inducible Costimulator Gene-Transduced Bone Marrow-Derived Mesenchymal Stem Cells Attenuate the Severity of Acute Graft-Versus-Host Disease in Mouse Models

Dan Yang, Li-Ping Wang, Hong Zhou, Hui Cheng, Xiao-Chen Bao, Sheng Xu, Wei-Ping Zhang, and Jian-Min Wang

Institute of Hematology, Changhai Hospital, the Second Military Medical University, Shanghai, China

In murine allogeneic transplantation models, ICOS gene-transduced bone marrow-derived mesenchymal stem cells (MSCsICOS-EGFP) were evaluated for their effects on GvHD severity and long-term survival. Lethally irradiated BALB/c or first filial generation of BALB/c and C57BL/6 (CB6F1) mice were transplanted with bone marrow cells and splenocytes from C57BL/6 mice to establish acute GvHD models. Recipient mice were injected with MSCsICOS-EGFP, MSCs, MSCsEGFP, ICOS-Ig fusion protein, MSCs + ICOS-Ig, or PBS (control group). Long-term survival, GvHD rates and severity, CD4+
T-cell apoptosis and proliferation, and Th1/Th2/Th17 effecter cell polarization were evaluated. In the C57BL/6 → CB6F1 HSCT model, the long-term survival in the MSCICOS-EGFP group was higher than that in the GvHD group (74.29 ± 7.39% vs. 0, p < 0.01), and this survival rate was also higher than that in the MSC, ICOS-Ig, or MSC + ICOS-Ig groups (42.86 ± 8.36%, p = 0.004; 48.57 ± 8.45%, p = 0.03; or 50.43 ± 8.45% p = 0.04, respectively). The survival advantages of MSCICOS-EGFP-treated group were confirmed in the C57BL/6 ® BALB/c HSCT model. In both HSCT models, the low mortality in the MSCICOS-EGFP group was associated with lower incidence and severity of acute GvHD. Treatment with MSCsICOS-EGFP induced more CD4+ T-cell apoptosis compared with that in the GvHD group. The effect on CD4+ T cells was shown as early as day 2 and maintained until day 14 (p < 0.05 on days 2, 3, 7, and 14). Furthermore, we demonstrated that MSCsICOS-EGFP were able to suppress Th1 and Th17 polarization and promote Th2 polarization on both protein expression and gene transcription levels. Higher serum levels of IL-4, IL-10, and lower levels of IFN-g, IL-2, IL-12, and IL-17A were detected in the MSCICOS-EGFP group. The MSCsICOS-EGFP could also induce GATA-3, STAT6 expression and inhibit T-bet, STAT4, ROR-γt expression. Our results showed that injection of MSCsICOS-EGFP is a promising strategy for acute GvHD prevention and treatment. It provides synergistic benefits of MSC immune modulation and ICOS-B7h pathway blockage.

Key words: Mesenchymal stem cells (MSCs); Inducible costimulator (ICOS); Graft-versus-host disease (GvHD); Th1/Th2/Th17 polarization

Received January 22, 2014; final acceptance September 3, 2014. Online prepub date: September 8, 2014.
Address correspondence to Jian-Min Wang, Institute of Hematology, Changhai Hospital, the Second Military Medical University, Shanghai 200433, China. Tel: +86-21- 31161280; Fax: +86-21-31161293; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1733-1752, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X684033
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Human Amniotic Membrane-Derived Mesenchymal and Epithelial Cells Exert Different Effects on Monocyte-Derived Dendritic Cell Differentiation and Function

Marta Magatti,* Maddalena Caruso,* Silvia De Munari,* Elsa Vertua,* Debashree De,* Ursula Manuelpillai,†‡1 and Ornella Parolini*1

*Centro di Ricerca E. Menni, Fondazione Poliambulanza-Istituto Ospedaliero, Brescia, Italy
†Monash Institute of Medical Research-Prince Henry’s Institute and Monash University, Clayton, Australia
‡Pregnancy Research Centre, Royal Women’s Hospital, Parkville, Australia

We previously demonstrated that mesenchymal cells from human amniotic membrane (hAMTCs) inhibit the generation and maturation of monocyte-derived dendritic cells (DCs) in vitro. Considering the crucial role of DCs in the immune response and that epithelial cells of the human amniotic membrane (hAECs) share some of the immunoregulatory properties of hAMTCs, we investigated whether hAECs also modulate monocytederived DCs. We compared hAECs with hAMTCs in a cell-to-cell contact setting and their secreted factors in modulating DC differentiation and function. First, we demonstrated that primary and expanded hAMTCs strongly inhibited the differentiation of DCs and induced a shift toward M2-like macrophages. This was observed whenhAMTCs were cultured in contact (hAMTC-DCcont) or in Transwells (hAMTC-DCtw) with monocytes and even when medium conditioned by hAMTCs was used instead of hAMTCshAECs also prevented DC development, but to a lesser extent thanhAMTCshAECs were more effective when cultured in contact with monocytes (hAEC-DCcont) rather than in Transwells (hAEC-DCtw). The modulatory capacity of hAECs changed during passaging unlike the hAMSCs. The ability to stimulate CD4+
and CD8+ T-cell proliferation was almost completely abolished by hAMTC-DCcont, whereas hAMTC-DCtw and hAEC-DCcont displayed only a reduced ability to stimulate CD8+ T cells. Furthermore, monocytes cocultured with hAMTCs and hAECs showed some similarities, but also differences in cytokine/chemokine secretion. Similarities were observed in the inhibition of IL-12p70 and TNF-α and the increase in IL-10 in supernatants taken from monocyte-DCs cocultured with hAMTCs and hAECs in contact andTranswell settings. The inflammatory factors IL-8, CXCL9, and MIP-1α were significantly lower in hAMTC-DCconthAMTC-DCtw, and hAEC-DCcont conditions. In contrast, only hAMTCs (in both contact and Transwell conditions) were able to significantly increase IL-1β and CCL2. Altogether, we demonstrated that hAMTCs and hAECs affect DC differentiation, but that hAMTCs exerted a stronger inhibitory effect, abolished T-cell proliferation, and also induced more changes in cytokine/chemokine production.

Key words: Amniotic mesenchymal stromal cells; Amniotic epithelial cells (AECs); Dendritic cells (DCs); Monocytes; Human placenta; Immunomodulation

Received April 4, 2014; final acceptance August 11, 2014. Online prepub date: August 19, 2014.
1These authors provided equal contribution to this work.
Address correspondence to Ornella Parolini, Ph.D., Centro di Ricerca “E. Menni”, Fondazione Poliambulanza Istituto Ospedaliero, Via Bissolati, 57 I-25124 Brescia, Italy. Tel: ++390303518904; Fax: ++390303518915; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1753-1765, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X683502
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Trophic Effects and Regenerative Potential of Mobilized Mesenchymal Stem Cells From Bone Marrow and Adipose Tissue as Alternative Cell Sources for Pulp/Dentin Regeneration

Masashi Murakami,* Yuki Hayashi,*† Koichiro Iohara,* Yohei Osako,* Yujiro Hirose,*‡ and Misako Nakashima*

*Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, Obu, Japan
†Department of Pediatric Dentistry, School of Dentistry, Aichi-gakuin University, Nagoya, Japan
‡Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan

Dental pulp stem cell (DPSC) subsets mobilized by granulocyte-colony-stimulating factor (G-CSF) are safe and efficacious for complete pulp regeneration. The supply of autologous pulp tissue, however, is very limited in the aged. Therefore, alternative sources of mesenchymal stem/progenitor cells (MSCs) are needed for the cell therapy. In this study, DPSCs, bone marrow (BM), and adipose tissue (AD)-derived stem cells of the same individual dog were isolated using G-CSF-induced mobilization (MDPSCs, MBMSCs, and MADSCs). The positive rates of CXCR4 and G-CSFR in MDPSCs were similar to MADSCs and were significantly higher than those in MBMSCs. Trophic effects of MDPSCs on angiogenesis, neurite extension, migration, andantiapoptosis were higher than those of MBMSCs and MADSCs. Pulp-like loose connective tissues were regenerated in all three MSC transplantations. Significantly higher volume of regenerated pulp and higher density of vascularization and innervation were observed in response to MDPSCs compared to MBMSC and MADSC transplantation. Collagenous matrix containing dentin sialophosphoprotein (DSPP)-positive odontoblast-like cells was the highest in MBMSCs and significantly higher in MADSCs compared to MDPSCs. MBMSCs and MADSCs, therefore, have potential for pulp regeneration, although the volume of regenerated pulp tissue, angiogenesis, and reinnervation, were less. Thus, in conclusion, an alternative cell source for dental pulp/dentin regeneration are stem cells from BM and AD tissue.

Key words: Dental pulp stem/progenitor cells; Bone marrow-derived stem cells (BMSCs); Adipose-derived stem cells (ADSCs); Granulocyte-colony-stimulating factor (G-CSF); Trophic effect; Pulp/dentin regeneration

Received May 20, 2014; final acceptance July 26, 2014. Online prepub date: July 30, 2014.
Address correspondence to Misako Nakashima, Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, 35 Gengo, Morioka, Obu, Aichi 474-8511, Japan. Tel: +81 562 44 5651×5065; Fax: +81 562 46 8684; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1767-1779, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X684628
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Synergistic Effects of a Calcium Phosphate/Fibronectin Coating on the Adhesion of Periodontal Ligament Stem Cells Onto Decellularized Dental Root Surfaces

Jung-Seok Lee,*1 Hyun-Suk Kim,*1 So-Yon Park,† Tae-Wan Kim,* Jae-Suk Jung,* Jong-Bin Lee,* and Chang-Sung Kim†

*Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Republic of Korea
†Department of Periodontology, Research Institute for Periodontal Regeneration, BK21 PLUS Project, College of Dentistry, Yonsei University, Seoul, Republic of Korea

This study aimed to enhance the attachment of periodontal ligament stem cells (PDLSCs) onto the decellularized dental root surface using surface coating with fibronectin and/or calcium phosphate (CaP) and to evaluate the activity of PDLSCs attached to a coated dental root surface following tooth replantation. PDLSCs were isolated from five dogs, and the other dental roots were used as a scaffold for carrying PDLSCs and then assigned to one of four groups according to whether their surface was coated withCaP, fibronectin, CaP/fibronectin, or left uncoated (control). Fibronectin increased the adhesion of PDLSCs onto dental root surfaces compared to both the control and CaP-coated groups, and simultaneous surface coating with CaP and fibronectin significantly accelerated and increased PDLSC adhesion compared to the fibronectin-only group. On in vivo tooth replantation, functionally oriented periodontal new attachment was observed on the CaP/fibronectin-coated dental roots to which autologous PDLSCs had adhered, while in the control condition, dental root replantation was associated only with root resorption and ankylosis along the entire root length. CaP and fibronectin synergistically enhanced the attachment of PDLSCs onto dental root surfaces, and autologous PDLSCs could produce de novo periodontal new attachment in an experimental in vivo model.

Key words: Cell adhesion; Calcium phosphate; Fibronectin; Periodontium; Stem cell; Surface treatment

Received May 16, 2014; final acceptance September 8, 2014. Online prepub date: October 6, 2014.
1These authors provided equal contribution to this work.
Address correspondence to Chang-Sung Kim, Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, 50-1, Yonsei-roSeodeamun-gu, Seoul 120-752, Republic of Korea. Tel: +82-2-22283185; Fax: +82-2-39203981; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1781-1797, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X684042
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Beneficial Effect of Human Induced Pluripotent Stem Cell-Derived Neural Precursors in Spinal Cord Injury Repair

Nataliya Romanyuk,* Takashi Amemori,* Karolina Turnovcova,* Pavel Prochazka,* Brigitte Onteniente,†‡ Eva Sykova,*§ and Pavla Jendelova

*Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic
†INSERM UMR 861, 91030 Evry cedex, France
Universite Evry-Val d’Essonne, 91030 Evry cedex, France
§Department of Neuroscience, Charles University, Second Faculty of Medicine, Prague, Czech Republic

Despite advances in our understanding and research of induced pluripotent stem cells (iPSCs), their use in clinical practice is still limited due to lack of preclinical experiments. Neural precursors (NPs) derived from a clone of human iPSCs (IMR90) were used to treat a rat spinal cord lesion 1 week after induction. Functional recovery was evaluated using the BBB, beam walking, rotarod, and plantar tests. Lesion morphology, endogenous axonal sprouting, graft survival, and iPSC-NP differentiation were analyzed immunohistochemically. Quantitative polymerase chain reaction (qPCR) was used to evaluate the effect of transplanted iPSC-NPs on endogenous regenerative processes and also to monitor their behavior after transplantation. Human iPSC-NPs robustly survived in the lesion, migrated, and partially filled the lesion cavity during the entire period of observation. Transplanted animals displayed significant motor improvement already from the second week after the transplantation of iPSC-NPs. qPCR revealed the increased expression of human neurotrophins 8 weeks after transplantation. Simultaneously, the white and gray matter were spared in the host tissue. The grafted cells were immunohistochemically positive for doublecortin, MAP2, βIII-tubulin, GFAP, andCNPase 8 weeks after transplantation. Human iPSC-NPs further matured, and 17 weeks after transplantation differentiated toward interneurons, dopaminergic neurons, serotoninergic neurons, and ChAT-positive motoneurons. Human iPSCNPs possess neurotrophic properties that are associated with significant early functional improvement and the sparing of spinal cord tissue. Their ability to differentiate into tissue-specific neurons leads to the long-term restoration of the lesioned tissue, making the cells a promising candidate for future cell-based therapy of SCI.

Key words: Human induced pluripotent stem cells; Neural precursors (NPs); Spinal cord injury; Neuronal differentiation; Trophic support; Neuroregeneration

Received May 7, 2013; final acceptance August 14, 2014. Online prepub date: August 19, 2014.
Address correspondence to Pavla Jendelova, Institute of Experimental Medicine ASCR, Videnska 1083, 142 20 Prague 4, Czech Republic. Tel: +420 241 062 282; Fax: +420 241 062 706; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1799-1812, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X684079
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Transplanted Human Induced Pluripotent Stem Cell-Derived Neural Progenitor Cells Do Not Promote Functional Recovery of Pharmacologically Immunosuppressed Mice With Contusion Spinal Cord Injury

Yuriy Pomeshchik,* Katja A. Puttonen,* Iurii Kidin,* Marika Ruponen,*† Sarka Lehtonen,* Tarja Malm,* Elisabet Akesson,‡ Outi Hovatta,§ and Jari Koistinaho*

*Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
†School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
‡Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
§Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden

Improved functional recovery after spinal cord injury by transplantation of induced pluripotent stem cell-derived neural stem/progenitor cells (iPSC-NPCs) has been reported. However, beneficial effects of iPSC-based therapy have so far been produced mostly using genetically immunodeficient rodents. Because of the long time required for generation and characterization of iPSCs, the use of autologous iPSCs for treating patients with acute spinal cord injury (SCI) is not feasible. Therefore, it is of utmost importance to investigate the effect of iPSC-based therapy on functional recovery after SCI using pharmacologically immunosuppressed, immunocompetent animal models. Here we studied the functional outcome following subacute transplantation of human iPSC-derived NPCs into contused mouse spinal cord when tacrolimus was used as an immunosuppressive agent. We show that human iPSC-derived NPCs transplanted into pharmacologically immunosuppressed C57BL/6J mice exhibited poor long-term survival and failed to improve functional recovery after SCI as measured by Basso Mouse Scale (BMS) for locomotion and CatWalk gait analysis when compared to vehicle-treated animals. The scarce effect of iPSC-based therapy observed in the current study may be attributable to insufficient immunosuppressive effect, provided by monotherapy with tacrolimus in combination with immunogenicity of transplanted cells and complex microenvironment of the injured spinal cord. Our results highlight the importance of extensive preclinical studies of transplanted cells before the clinical application of iPSC-based cell therapy is achieved.

Key words: Spinal cord injury (SCI); Induced pluripotent stem cells; Cell transplantation; Immunosuppression; Tacrolimus

Received February 4, 2014; final acceptance September 1, 2014. Online prepub date: September 8, 2014.
Address correspondence to Dr. Jari Koistinaho, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland. Tel: +358403552427; Fax: +35817163030; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1813-1827, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X683025
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
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Intrathecal Transplantation of Autologous Adherent Bone Marrow Cells Induces Functional Neurological Recovery in a Canine Model of Spinal Cord Injury

Hala Gabr,* Wael Abo El-kheir,† Haithem A. M. A. Farghali,‡ Zeinab M. K. Ismail,§ Maha B. Zickri,§ Zeinab M. El Maadawi,§ Nirmeen A. Kishk,¶ and Hatem E. Sabaawy*#

*Department of Hematology, Faculty of Medicine, Cairo University, Cairo, Egypt
†Department of Immunology, Military Medical Academy, Cairo, Egypt
‡Department of Veterinary Surgery, Anesthesiology and Radiology, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt
§Department of Histology, Faculty of Medicine, Cairo University, Cairo, Egypt
¶Department of Neurology, Faculty of Medicine, Cairo University, Cairo, Egypt
#Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, and Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

Spinal cord injury (SCI) results in demyelination of surviving axons, loss of oligodendrocytes, and impairment of motor and sensory functions. We have developed a clinical strategy of cell therapy for SCI through the use of autologous bone marrow cells for transplantation to augment remyelination and enhance neurological repair. In a preclinical large mammalian model of SCI, experimental dogs were subjected to a clipping contusion of the spinal cord. Two weeks after the injury, GFP-labeled autologous minimally manipulated adherent bone marrow cells (ABMCs) were transplanted intrathecally to investigate the safety and efficacy of autologous ABMC therapy. The effects of ABMC transplantation in dogs with SCI were determined using functional neurological scoring, and the integration of ABMCs into the injured cords was determined using histopathological and immunohistochemical investigations and electron microscopic analyses of sections from control and transplanted spinal cords. Our data demonstrate the presence of GFP-labeled cells in the injured spinal cord for up to 16 weeks after transplantation in the subacute SCI stage. GFP-labeled cells homed to the site of injury and were detected around white matter tracts and surviving axons. ABMC therapy in the canine SCI model enhanced remyelination and augmented neural regeneration, resulting in improved neurological functions. Therefore, autologous ABMC therapy appears to be a safe and promising therapy for spinal cord injuries.

Key words: Autologous adherent bone marrow-derived cell therapy; Spinal cord injury (SCI); Canine; Intrathecal; Remyelination

Received May 10, 2012; final acceptance July 10, 2014. Online prepub date: July 15, 2014.
Address Correspondence to Hatem E. Sabaawy, M.D., Ph.D., Regenerative and Molecular Medicine Program, Rutgers-Robert Wood Johnson Medical School, 195 Little Albany Street, New Brunswick, NJ 08901, USA. Tel: +1-732-235-8081; Fax: +1-732-235-8681; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1829-1844, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X684583
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

βB2-Crystallin Promotes Axonal Regeneration in the Injured Optic Nerve in Adult Rats

Michael R. R. Bohm,*†1 Verena Prokosch,*1 Matthias Bruckner,* Sarah Pfrommer,* Harutyun Melkonyan,* and Solon Thanos*†

*Institute for Experimental Ophthalmology, School of Medicine, University of Munster, Albert-Schweitzer-Campus 1, Munster, Germany
†Interdisciplinary Center for Clinical Research, School of Medicine, University of Munster, Albert-Schweitzer-Campus 1, Munster, Germany

The purpose of the study was to further scrutinize the potential of βB2-crystallin in supporting regeneration of injured retinal ganglion cell axons both in vitro and in vivo. Retinal explants obtained from animals after treatment either with lens injury (LI) alone or with combined LI 5 days or 3 days before or simultaneously with an optic nerve crush (ONC) were cultured for 96 h under regenerative conditions, and the regenerating axons were quantified and compared with untreated controls. These measurements were then repeated with LI replaced by intravitreal injections of γ-crystallin and β-crystallin at 5 days before ONC. Finally, βB2-crystallinoverexpressing transfected neural progenitor cells (βB2-crystallin-NPCs) in the eye were studied after crushing the optic nerve in vivo. Regeneration was monitored with the aid of immunoblotting of the retina and optic nerve both distal and proximal to the lesion site, and this was compared with controls that received injections of phosphate buffer only. LI performed 5 days or 3 days before ONC significantly promoted axonal outgrowth in vitro (p < 0.001), while LI performed alone before explantation did not. Intravitreal injections of β-crystallin and γ-crystallin mimicked the effects of LI and significantly increased axonal regeneration in culture at the same time intervals (p < 0.001). Western blot analysis revealed that crystallins were present in the proximal optic nerve stump at the lesion site in ONC, but were neither expressed in the undamaged distal optic nerve nor in uninjured tissue. βB2-crystallin-NPCs supported the regeneration of cut optic nerve axons within the distal optic nerve stump in vivo. The reported data suggest that βB2-crystallin-producing “cell factories” could be used to provide novel therapeutic drugs for central nervous system injuries.

Key words: Axonal regeneration; Crystallins; Optic nerve crush; Embryonic neural progenitor cells (NPCs)

Received February 28, 2014; final acceptance September 2, 2014. Online prepub date: October 8, 2014.
1These authors provided equal contribution to this work.
Address correspondence to Michael R. R. Bohm, Institute for Experimental Ophthalmology, School of Medicine, University of Munster, Albert-Schweitzer-Campus 1, D15, 48149 Munster, Germany. Tel: +49-251-8356040; Fax: +49-251-8356916; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1845-1861, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X685069
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Ex Vivo Propagation of Human Corneal Stromal “Activated Keratocytes” for Tissue Engineering

Gary Hin-Fai Yam,*§ Nur Zahirah Binte M. Yusoff,* Aishwarya Kadaba,* Dechao Tian,† Htoon Hla Myint,‡§ Roger W. Beuerman,§¶# Lei Zhou,§¶# and Jodhbir S. Mehta*‡§#

*Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute, Singapore
†Department of Statistics and Applied Probability, National University of Singapore
‡Singapore National Eye Centre, Singapore
§Duke-NUS Graduate Medical School, Singapore
¶Ocular Proteomics Group, Singapore Eye Research Institute, Singapore
#Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Keratoconus is a corneal disorder characterized by a thinning of stromal tissue, and the affected patients have induced astigmatism and visual impairment. It is associated with a loss of corneal stromal keratocytes (CSKs). Hence, reconstructing stromal tissue with autologous CSK replacement can be a viable alternative to corneal transplantation, which is restricted by the global donor material shortage and graft rejection. Human CSKs are normally quiescent and express unique markers, like aldehyde dehydrogenases and keratocan. In serum culture, they proliferate, but lose their characteristic phenotype and become stromal fibroblasts. Here we report a novel culture cocktail to ex vivo propagate and maintain CSKs. Primary human CSKs were obtained from adult donors and cultured with soluble human amnion stromal extract (ASE), rho-associated coiled-coil-forming protein serine/threonine kinase inhibitor Y-27632, and insulin-like growth factor-1 (collectively named as ERI). Protein profiling using mass spectrometry followed by MetaCore™ pathway analysis predicted that ASE proteins might participate in transforming growth factor-β (TGF-β) signaling and fibroblast development, cell adhesion, extracellular matrix remodeling, and immune response. In culture with 0.5% fetal bovine serum and ERI, the population of “activated keratocytes” was expanded. They had much lowered expression of both keratocyte and fibroblast markers, suppressed TGF-β-mediated Smad2/3 activation, and lacked fibroblast-mediated collagen contractibility. These “activated keratoctyes” could be propagated for six to eight passages ex vivo, and they regained CSK-specific dendritic morphology and gene marker expression, including aldehyde dehydrogenases, lumican, andkeratocan biosynthesis, expression, and secretion when returned to serum-depleted ERI condition. This novel cocktail maintained human CSKs in both adherent and suspension cultures with proper keratocyte features and without the transformation to stromal fibroblasts. Thus, human CSKs can be ex vivo propagated as transient “activated keratocytes.” This could provide sufficient number of genuine CSKs for corneal tissue engineering.

Key words: Cornea; Stromal keratocytes; Amnion stromal extract (ASE); Proliferation

Received January 24, 2014; final acceptance September 10, 2014. Online prepub date: October 6, 2014.
Address correspondence to Assoc. Prof. Jodhbir S. Mehta, Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute, 11, Third Hospital Avenue, Singapore National Eye Center Building #08/00, Singapore 168751. Tel: +65 62277255; Fax: +65 62277290; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1863-1877, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X681045
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Donor Pretreatment With IL-1 Receptor Antagonist Attenuates Inflammation and Improves Functional Potency in Islets From Brain-Dead Nonhuman Primates

Juan S. Danobeitia,* Matthew S. Hanson,* Peter Chlebeck,* Elisa Park,* Jamie M. Sperger,* Alice Schwarznau,*† and Luis A. Fernandez*

*Department of Surgery-Division of Transplantation, University of Wisconsin-Madison, Madison, WI, USA
†Department of Surgery, Hospital Grosshadern, Ludwig-Maximilian’s University, Munich, Germany

Most pancreas and islet grafts are recovered from brain-dead (BD) donors. In this study we characterized the early inflammatory response induced by brain death in pancreata and islets from nonhuman primate donors and evaluated the effect of targeted anti-inflammatory intervention in the protection of pancreatic islets prior to transplantation. BD donors were monitored for 6 h and assigned to three experimental groups: group 1: BD-untreated donors (BD-UT) (n = 7), group 2: BD + donor pretreatment with IL-1ra (n = 6), and group 3: non-BD animals serving as controls (n = 7). We observed an IL-1ra-dependent reduction in the mobilization and activation of neutrophils from bone marrow and a significantly reduced accumulation of CD68
+ leukocytes in the pancreas and islets after brain death induction. Donor treatment with IL-1ra significantly decreased chemokine mRNA expression (MCP-1, IL-8, and MIP-1a) and attenuated the activation of circulating neutrophils and intraislet macrophages as demonstrated by a reduction in intracellular IL-1β, IL-6, MCP-1, and MIP-1a expression. As a result, IL-1ra dramatically improved viability, mitochondrial membrane polarity, and islet engraftment in mice transplanted using a minimal islet mass. These results suggest that early immunomodulation targeting inflammation in the BD donor may represent an effective therapeutic strategy to improve islet quality and function prior to transplantation.

Key words: Islet transplantation; Brain death; IL-1 receptor antagonist; Donor management; Innate immunity; Inflammation

Received December 19, 2013; final acceptance April 14, 2014. Online prepub date: April 22, 2014.
Address correspondence to Luis A. Fernandez, M.D., Department of Surgery, Division of Transplantation, University of Wisconsin-Madison School of Medicine and Public Health, H4/782 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA. Tel: +1-608-263-9903; Fax: +1-608-626-6280; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1879-1886, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X683548
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Human Pancreatic Islets Isolated From Donors With Elevated HbA1c Levels: Islet Yield and Graft Efficacy

Meirigeng Qi, Brian McFadden, Luis Valiente, Keiko Omori, Shiela Bilbao, Jemily Juan, Jeffrey Rawson, Alina R. Oancea, Stephen Scott, Indu Nair, Kevin Ferreri, Yoko Mullen, Donald Dafoe, Mohamed EI-Shahawy, Fouad Kandeel, and Ismail H. Al-Abdullah

Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute of the City of Hope, Duarte, CA, USA

The aim of this study was to investigate the effects of elevated donor HbA1c levels (type 2 diabetes, T2D) on the islet yield and functionality postisolation. In this retrospective analysis, donors for islet isolations were classified into two groups: T2D group (HbA1c ≥ 6.5%, n = 18) and normal group (HbA1c < 6.5%, n = 308). Optimum pancreas digestion time (switch time) was significantly higher in the T2D group compared to the normal group (13.7 ± 1.2 vs. 11.7 ± 0.1 min, respectively, p = 0.005). Islet yields were significantly lower in the T2D group compared to the control (T2D vs. control): islet equivalent (IEQ)/g (prepurification 2,318 ± 195 vs. 3,713 ± 114, p = 0.003; postpurification 1,735 ± 175 vs. 2,663 ± 89, p = 0.013) and islet particle number (IPN)/g (prepurification, 2,519 ± 336 vs. 4,433 ± 143, p = 0.001; postpurification, 1,760 ± 229 vs. 2,715 ± 85, p = 0.007). Islets from T2D pancreata had significantly lower viability (T2D vs. control: 91.9 ± 1.6 vs. 94.4 ± 0.3%, p = 0.004) and decreased oxygen consumption rate (DOCR) (T2D vs. control: 0.09 ± 0.01 and 0.21 ± 0.03 nmol O2
100 islets−1 min−1p = 0.049). The islets isolated from T2D donor pancreata reversed diabetes in NOD-SCID mice in 9% (2/22) compared to islets from control donor pancreata, which reversed diabetes in 67% (175/260, p < 0.001). In conclusion, this study demonstrates that elevated HbA1c (≥6.5%) is associated with impairment of islet function and lower islet yield; however, these islets could not be suitable for clinical applications.

Key words: Transplantation; Islet isolation; HbA1c; Type 2 diabetes; NOD-SCID

Received April 11, 2014; final acceptance July 29, 2014. Online prepub date: August 5, 2014.
Address correspondence to Ismail H. Al-Abdullah, Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute of the City of Hope, 1500 E. Duarte Rd, Duarte, CA 91010, USA. Tel: +1-626-256-4673, ext. 60109; Fax: +1-626-256-8704; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1887-1900, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X683494
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Syngeneic Myoblast Transplantation Improves Muscle Function in a Murine Model of X-Linked Myotubular Myopathy

Hyun Ju Lim,* Sunyoung Joo,* Seh-Hoon Oh,*† John D. Jackson,* Delrae M. Eckman,*‡ Tiffaney M. Bledsoe,* Christopher R. Pierson Martin K. Childers,*¶ Anthony Atala,* and James J. Yoo*

*Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC, USA
†Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA
‡Biomedical Sciences Program, College of Health Sciences, Midwestern University, Glendale, AZ, USA
§Research Institute, Nationwide Children’s Hospital and Department of Pathology, Ohio State University College of Medicine, Columbus, OH, USA
¶Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA

X-linked myotubular myopathy (XLMTM) is an isogenic muscle disease characterized by progressive wasting of skeletal muscle, weakness, and premature death of affected male offspring. Recently, the XLMTM gene knock-in mouse, Mtm1 p.R69C, was found to have a similar phenotype as the MTM1 gene mutation in humans (e.g., central nucleation of small myofibers, attenuated muscle strength, and motor unit potentials). Using this rodent model, we investigated whether syngeneic cell therapy could mitigate muscle weakness. Donor skeletal muscle-derived myoblasts were isolated from C57BL6 wild-type (WT) and Mtm1 p.R69C (KI) mice for transplantation into the gastrocnemius muscle of recipient KI mice. Initial experiments demonstrated that donor skeletal muscle-derived myoblasts from WT and KI mice remained in the gastrocnemius muscle of the recipient KI mouse for up to 4 weeks posttransplantation. KI mice receiving syngeneic skeletal muscle-derived myoblasts displayed an increase in skeletal muscle mass, augmented force generation, and increased nerve-evoked skeletal muscle action potential amplitude. Taken together, these results support our hypothesis that syngeneic cell therapy may potentially be used to ameliorate muscle weakness and delay the progression of XLMTM, as application expands to other muscles.

Key words: X-linked myotubular myopathy (XLMTM); Myoblast; Syngeneic cell transplantation; Muscle regeneration; Muscle physiologic functions

Received September 23, 2013; final acceptance July 18, 2014. Online prepub date: July 25, 2014.
Address correspondence to James J. Yoo, M.D., Ph.D., Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Tel: +1-336-713-7294; Fax: +1-336-713-7290; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Transplantation, Vol. 24, pp. 1901-1911, 2015
0963-6897/15 $90.00 + .00
DOI: http://dx.doi.org/10.3727/096368914X683520
E-ISSN 1555-3892
Copyright © 2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Safety and Feasibility of Remote Limb Ischemic Preconditioning in Patients With Unilateral Middle Cerebral Artery Stenosis and Healthy Volunteers

Sijie Li,* Chun Ma,† Guo Shao,† Fatema Esmail,‡ Yang Hua,§ Lingyun Jia,§ Jian Qin,* Changhong Ren,† Yumin Luo,† Yuchun Ding,‡ Cesario V. Borlongan,¶ and Xunming Ji†#

*Emergency Department, Xuan Wu Hospital, Capital Medical University, Beijing, China
†Institute of Hypoxia Medicine, Xuan Wu Hospital, Capital Medical University, Beijing, China
‡Department of Neurosurgery, Wayne State University School of Medicine, Detroit, USA
§Vascular Ultrasound Division, Xuan Wu Hospital, Capital Medical University, Beijing, China
¶Department of Neurosurgery and Brain Repair, University of South Florida, Morsani College of Medicine, Tampa, FL, USA
#Department of Neurosurgery, Xuan Wu Hospital, Capital Medical University, Beijing, China

Previous studies have indicated a neuroprotective effect of remote limb ischemic preconditioning. The aim of the present study was to assess whether upper arm ischemic preconditioning is feasible and safe in patients with unilateral middle cerebral artery (MCA) stenosis compared to healthy volunteers. Ten patients with unilateral MCA stenosis and 24 healthy volunteers underwent limb ischemic preconditioning, consisting of five cycles of 5-min inflations of a blood pressure cuff to 200 mmHg around an upper limb followed by 5 min of reperfusion. Limb ischemic preconditioning has no significant effect on the heart rate, oxygenation index, or mean flow velocity in patients with unilateral MCA stenosis or healthy volunteers. However, healthy volunteers showed a reduction in blood pressure 30 min following reperfusion of the last cycle. Limb ischemic preconditioning was found to be safe and well tolerated in both patients and healthy volunteers. We highlight the potential of limb ischemic preconditioning as an adjunct to neuroprotective treatment.

Key words: Ischemic preconditioning (IPC); Blood pressure (BP); Middle cerebral artery (MCA) stenosis; Clinical trial; Stem cells

Received June 6, 2014; final acceptance July 28, 2014. Online prepub date: July 30, 2014.
Address correspondence to Dr. Xunming Ji, Professor of Neurosurgery, VP of Xuan Wu Hospital, CMU, Changchun Street, No. 45, Xicheng District, Beijing, China. Tel: +8610 83198952; Fax: +8610 83154745; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it