Cell Medicine 2(2) Abstracts

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Cell Medicine, Part B of Cell Transplantation, Vol. 2, pp. 43–53, 2010
2155-1790/10 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517911X593100
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved


Review

Mesenchymal Stromal Cells as a Therapeutic Strategy to Support Islet Transplantation in Type 1 Diabetes Mellitus

Sarah A. Busch,* Saskia T. J. van Crutchen,† Robert J. Deans,* and Anthony E. Ting*

*Athersys, Inc., Department of Regenerative Medicine, Cleveland, OH, USA
†ReGenesys, Department of Regenerative Medicine, Leuven, Belgium

Type 1 diabetes is an autoimmune disorder that leads to destruction of pancreatic b islet cells and is a growing global health issue. While insulin replacement remains the standard therapy for type 1 diabetes, exogenous insulin does not mimic the physiology of insulin secretion. Transplantation of pancreatic islets has the potential to cure this disease; however, there are several major limitations to widespread implementation of islet transplants. The use of mesenchymal stromal cells (MSCs) in the treatment of type 1 diabetes has been investigated as an adjunct therapy during islet graft administration to prevent initial islet loss and promote engraftment and revascularization of islets. In this review we will discuss the results of recent MSC studies in animal models of diabetes with a focus on islet transplantation and explore the potential for these findings to be extended to clinical use for the treatment of type 1 diabetes.

Key words: Type 1 diabetes; Islet transplantation; Bone marrow; Mesenchymal stromal cell (MSCs); Immunomodulation

Address correspondence to Anthony Ting, Athersys, Inc., Department of Regenerative Medicine, 3201 Carnegie Avenue, Cleveland, OH 44115, USA. Tel: (216) 431-9900; Fax: (216) 361-9596; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Part B of Cell Transplantation, Vol. 2, pp. 55–67, 2010
2155-1790/10 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517911X582788
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Early Immunomodulation by Intravenously Transplanted Mesenchymal Stem Cells Promotes Functional Recovery in Spinal Cord Injured Rats

Jung Hwa Seo,*†1 In Keun Jang,‡1 Hyongbum Kim,§ Mal Sook Yang,‡ Jong Eun Lee,‡ Hyo Eun Kim,‡ Yong-Woo Eom,‡ Doo-Hoon Lee,‡ Ji Hea Yu,*†¶ Ji Yeon Kim,*†# Hyun Ok Kim,** and Sung-Rae Cho*†#

*Department & Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Korea
†Clinical Research Center, Yonsei University Health System, Seoul, Korea
‡Biomedical Research Institute, Lifeliver Inc, Suwon, Korea
§Graduate School of Biomedical Science and Engineering College of Medicine, Hanyang University, Seoul, Korea
¶Brain Korea 21 Project for Medical Science, Yonsei University, Seoul, Korea
#Graduate Program of Nano Science and Technology, Yonsei University, Seoul, Korea
**Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea

Although intravenous administration of mesenchymal stem cells (MSCs) can enhance functional recovery after spinal cord injury (SCI), the underlying mechanisms have to be elucidated. In this study, we explored the mechanisms for functional recovery in SCI rats after intravenous transplantation of MSCs derived from human umbilical cord blood. Sprague-Dawley rats were randomly assigned to receive either MSCs (1 ××106 cells/0.5 ml) or PBS into the tail vein immediately after SCI. They were then evaluated by the Basso-Beattie-Bresnahan (BBB) locomotor rating scale weekly for 8 weeks and by somatosensory evoked potentials (SSEPs) 8 weeks after transplantation. MSC-treated rats showed a modest but significant improvement in BBB scores and latencies of SSEPs, compared with PBS controls. When human-specific Alu element was measured in the spinal cord, it was detected only 1h after transplantation, suggesting transient engraftment of MSCs. Inflammatory cytokines were also determined using RT-PCR or Western blot in spinal cord extracts. In MSC-treated rats, the level of proinflammatory cytokine IL-1b was decreased, but that of anti-inflammatory cytokine IL-10 was increased. MSCs also immediately suppressed IL-6 at 1h posttransplantation. However, the response of IL-6, which has an immunoregulatory role, was increased 1–3 days after transplantation. In addition, we quantified microglia/macrophage stained with Iba-1 around the damaged spinal cord using immunohistochemistry. A proportion of activated microglia and macrophages in total Iba-1+ cells was significantly decreased in MSC-treated rats, compared with PBS controls. These results suggest that early immunomodulation by intravenously transplanted MSCs is a potential underlying mechanism for functional recovery after SCI.

Key words: Spinal cord injury; Transplantation; Mesenchymal stem cells (MSCs); Immunomodulation; Functional recovery

1These authors provided equal contribution to this work.
Address correspondence to Sung-Rae Cho M.D., Ph.D., Assistant Professor, Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, Korea 120-752. Tel: +82 2 2228-3715; Fax: +82 2 363-2795; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Part B of Cell Transplantation, Vol. 2, pp. 69–83, 2010
2155-1790/10 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517911X582779
Copyright © 2011 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Neuroprotective and Angiogenic Effects of Bone Marrow Transplantation Combined With Granulocyte Colony-Stimulating Factor in a Mouse Model of Amyotrophic Lateral Sclerosis

Yasuyuki Ohta, Makiko Nagai, Kazunori Miyazaki, Nobuhito Tanaka, Hiromi Kawai, Takafumi Mimoto, Nobutoshi Morimoto, Tomoko Kurata, Yoshio Ikeda, Tohru Matsuura, and Koji Abe

Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan

Bone marrow (BM) cells from amyotrophic lateral sclerosis (ALS) patients show significantly reduced expression of several neurotrophic factors. Monotherapy with either wild-type (WT) BM transplantation (BMT) or granulocyte colony-stimulating factor (GCSF) has only a small clinical therapeutic effect in an ALS mouse model, due to the phenomenon of neuroprotection. In this study, we investigated the clinical benefits of combination therapy using BMT with WT BM cells, plus GCSF after disease onset in ALS mice [transgenic mice expressing human Cu/Zn superoxide dismutase (SOD1) bearing a G93A mutation]. Combined treatment with BMT and GCSF delayed disease progression and prolonged the survival of G93A mice, whereas BMT or GCSF treatment alone did not. Histological study of the ventral horns of lumbar cords from G93A mice treated with BMT and GCSF showed a reduction in motor neuron loss coupled with induced neuronal precursor cell proliferation, increased expression of neurotrophic factors (glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, vascular endothelial growth factor and angiogenin), and neovascularization compared with controls (vehicle only). Compared with G93A microglial cells, most BM-derived WT cells differentiated into microglial cells and strongly expressed neurotrophic factors, combined BMT and GCSF treatment led to the replacement of G93A microglial cells with BM-derived WT cells. These results indicate combined treatment with BMT and GCSF has potential neuroprotective and angiogenic effects in ALS mice, induced by the replacement of G93A microglial cells with BM-derived WT cells. Furthermore, this is the first report showing the effects of combined BMT and GCSF treatment on blood vessels in ALS.

Key words: Bone marrow; Granulocyte colony-stimulating factor (GCSF); Superoxide dismutase (SOD1); Spinal cord; Amyotrophic lateral sclerosis (ALS)

Address correspondence to Prof. Koji Abe, Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. Tel: 81-86-235-7365; Fax: 81-86-235-7368; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it