Cell Medicine 8(3) Abstracts

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Cell Medicine, Vol. 8, pp. 63-77, 2016
2155-1790/16 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517916X
693366
Copyright © 2016 Cognizant, LLC.
Printed in the USA. All rights reserved

Allogeneic Mesenchymal Stem Cell Transplantation in Dogs With Keratoconjunctivitis Sicca

Maura K. W. Bittencourt,*1 Michele A. Barros,†1 João Flávio P. Martins,† Jose Paulo C. Vasconcellos,* Bruna P. Morais,† Celine Pompeia,‡ Matheus Domingues Bittencourt,§ Karine dos Santos Evangelho,¶ Irina Kerkis,‡ and Cristiane V. Wenceslau

*Department of Ophthalmology, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
Regenera Medicina Veterinária Avançada, Campinas, SP, Brazil
‡Instituto Butantan, São Paulo, SP, Brazil
§Private Practice Ophthalmologist, Benvista OftalmologiaIndaiatuba, São Paulo, SP, Brazil
¶Universidad Nacional de Rio Cuarto, Cordoba, Argentina

Keratoconjunctivitis sicca (KCS) is a dysfunction in tear production associated with clinical signs, which include conjunctival hyperemia, ocular discharge, discomfort, pain, and, eventually, corneal vascularization and pigmentation. Immunosuppressive drugs are routinely administrated for long periods to treat KCS but with side effects and limited results. Evaluation of the clinical benefits of intralacrimal transplantation of allogeneic mesenchymal stem cells (MSCs) in dogs with mild–moderate and severe KCS was done. A total of 24 eyes with KCS from 15 dogs of different breeds were enrolled in the present study. A single transplantation of MSCs (1 × 106) directly into lacrimal glands (dorsal and third eyelid) was performed. The Schirmer tear tests (STTs) and ocular surface improvements were used to assess short- and long-term effects of these cells. The STTs were carried out on day 0 (before MSCs transplantation) and on days 7, 14, 21, and 28, as well as 6 and 12 months after MSC transplantation. Our data demonstrate that allogeneic MSC transplantation in KCS dogs is safe since no adverse effects were observed immediately after transplantation and in short- and long-term follow-ups. A statistically significant increase in the STT and ocular surface improvements was found in all eyes studied. In all the eyes with mild–moderate KCS, STT values reverted to those of healthy eyes, while in eyes with severe KCS, although complete reversion was not found, there was improvement in tear production and in other clinical signs. Our study shows that a single dose of a low number of MSCs can be used to treat KCS in dogs. In contrast to immunosuppressive drug use, MSC transplantation has an effect over a long period (up to 12 months), even after a single administration, and does not require daily drug administration.

Key words: Allogeneic mesenchymal stem cell transplantation; Keratoconjunctivitis sicca (KCS); Dry eye syndrome; Schirmer tear test (STT); Dogs

Received August 8, 2016; final acceptance October 20, 2016. Online prepub date: October 18, 2016.
1These authors provided equal contribution to this work.
Address correspondence to Dr. Cristiane V. WenceslauLaboratório de Genética, Instituto Butantan, Av. Vital Brasil 1500, SP 05503-900, Brazil. Tel: +5511-26279703; Fax: +5511-26279581; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Dr. Irina KerkisLaboratório de Genética, Instituto Butantan, Av. Vital Brasil 1500, SP 05503-900, Brazil. Tel: +5511-26279703; Fax: +5511-26279581; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Vol. 8, pp. 79-85, 2016
2155-1790/16 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517916X693357
Copyright © 2016 Cognizant, LLC.
Printed in the USA. All rights reserved

αSMA Expression in Large Colonies of Colony-Forming Units-Fibroblast as an Early Predictor of Bone Marrow MSC Expandability

Irina Aizman,* William S. Holland,* Cher Yang,* and Damien Bates*†

*Department of Research, SanBio, Inc., Mountain View, CA, USA
†Clinical Development and Regulatory Affairs, SanBio, Inc., Mountain View, CA, USA

Clinical applications of mesenchymal stromal cells (MSCs) require the manufacture of large cell lots, which involves multiple passages for cell expansion and sometimes genetic modification. MSCs from various sources, including bone marrow (BM), exhibit high donor-to-donor variability in their growth characteristics. This can lead to unpredictable manufacturing outcomes with respect to success or failure of individual lots. Early determination of lot success has the potential to reduce the cost and improve the efficiency of the MSC manufacturing process. However, methods that effectively predict lot growth potential early in the manufacturing process are currently lacking. Here we report that the growth potential of an MSC lot can be predicted a few days after BM plating based on α-smooth muscle actin (αSMA) protein expression in large colony-forming unitfibroblast (CFU-f) colonies. The proposed prediction method could be a useful tool to prospectively determine MSC lot success or failure.

Key words: Mesenchymal stromal cells (MSCs); Colony-forming units-fibroblast (CFU-f); α-Smooth muscle actin (αSMA); Assay

Received August 24, 2016; final acceptance September 30, 2016. Online prepub date: October 6, 2016.
Address correspondence to Irina AizmanSanBio, Inc., 231 S. Whisman Road, Mountain View, CA 94041, USA. Tel: 650-625-8965; Fax: 650-625-8969; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Vol. 8, pp. 87-97, 2016
2155-1790/16 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517916X690486
Copyright © 2016 Cognizant, LLC.
Printed in the USA. All rights reserved

Stability Enhancement Using Hyaluronic Acid Gels for Delivery of Human Fetal Progenitor Tenocytes

A. Grognuz,* C. Scaletta,* A. Farron,† D. P. Pioletti,‡ W. Raffoul,* and L. A. Applegate*

*Unit of Regenerative Therapy, Service of Plastic, Reconstructive and Hand Surgery, Department of Musculoskeletal Medicine, University Hospital of Lausanne, Lausanne, Switzerland
†Service of Orthopaedics and Traumatology, Department of Musculoskeletal Medicine, University Hospital of Lausanne, Lausanne, Switzerland
‡Laboratory of Biomechanical Orthopedics, Institute of Bioengineering, EPFL, Lausanne, Switzerland

Tendon afflictions are very common, and their negative impact is high both at the workplace and in leisure activities. Tendinopathies are increasing in prevalence and can lead to tendon ruptures, where healing is a long process with outcomes that are often disappointing. Human fetal progenitor tenocytes (hFPTs) have been recently tested in vitro as a potential cell source to stimulate tendon regeneration. The aim of the present study was to compare different commercial hyaluronic acid (HA) gels, which could be used to resuspend hFPTs in a formulation that would allow for good delivery of the cells. No medium or growth supplement was used in the formulation in order to make it therapeutically dispensable. These conditions are stringent for cells, but surprisingly, we found that different formulations could allow a good survival for up to 3 days when stored at 4°C (refrigerator stable). The gels must allow a good survival of the cells in parallel with a good stability of the preparation over time and sufficient viscosity to remain in place if deposited on a wounded location. Moreover, the cells must conserve their ability to attach and to proliferate. hFPTs were able to survive and to recover from all of the tested gels, but some products showed some advantages over others in terms of survival and viscosity. Finally, the Ostenil Tendon HA gel fulfilled all of the requirements and presented the best compromise between a good survival and sufficient rheological characteristics to create an interesting cell delivery system.

Key words: Cell therapy; Hyaluronic acid gel; Tendon healing; Human fetal progenitor tenocytes (hFPTs); Cell stability

Received September 18, 2015; final acceptance February 23, 2016. Online prepub date: January 14, 2016.
Address correspondence to Professor Lee Ann Laurent-Applegate, University Hospital of Lausanne (CHUV), Service of Plastic, Reconstructive and Hand Surgery, Regenerative Therapy Unit (UTR), EPCR/Croisettes 22, CH-1066 Epalinges, Switzerland. Tel: +41-21-314-35-10; Fax: +41-21-887-84-14; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Cell Medicine, Vol. 8, pp. 99-112, 2016
2155-1790/16 $90.00 + .00
DOI: http://dx.doi.org/10.3727/215517916X692843
Copyright © 2016 Cognizant, LLC.
Printed in the USA. All rights reserved

Aggregation of Engineered Human β-Cells Into Pseudoislets: Insulin Secretion and Gene Expression Profile in Normoxic and Hypoxic Milieu

Marie-José Lecomte,* Séverine Pechberty,* Cécile Machado,* Sandra Da Barroca,* Philippe Ravassard,† Raphaël Scharfmann,‡§ Paul Czernichow,* and Bertrand Duvilli釧

*Univercell-Biosolutions, Centre de recherche des Cordeliers, Paris, France
†Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM)–Hôpital Pitié-Salpêtrière, Paris, France
‡INSERM U1016, Institut Cochin, Paris, France
§Université Paris Descartes, Sorbonne Paris CitéFaculté de Médecine, Paris, France

Innovative treatments to cure type 1 diabetes are being actively researched. Among the different strategies, the replacement of β-cells has given promising results. Classically, islets from cadaveric donors are transplanted into diabetic patients, but recently phase I clinical trials that use stem cell-derived β-cells have been started. Such protocols require either an immunosuppressive treatment or the macroencapsulation of the β-cells. They involve cell aggregation and the exposure of the cells to hypoxia. Using an engineered human β-cell, we have addressed these two problems: a novel human β-cell line called EndoC-βH3 was cultured as single cells or aggregated clusters. EndoC-βH3 cells were also cultured at normal atmospheric oxygen tension (pO2 = 21%) or hypoxia (pO2 = 3%) in the presence or absence of modulators of the hypoxia-inducible factor 1α (HIF1α) pathway. Cell aggregation improved glucose-stimulated insulin secretion, demonstrating the benefit of cell–cell contacts. Low oxygen tension decreased β-cell viability and their sensitivity to glucose, but did not alter insulin production nor the insulin secretion capacity of the remaining cells. To investigate the role of HIF1α, we first used a HIF stabilizer at pO2 = 21%. This led to a mild decrease in cell viability, impaired glucose sensitivity, and altered insulin secretion. Finally, we used a HIF inhibitor on EndoC-βH3 pseudoisletsexposed to hypoxia. Such treatment considerably decreased cell viability. In conclusion, aggregation of the EndoC-βH3 cells seems to be important to improve their function. A fraction of the EndoC-βH3 cells are resistant to hypoxia, depending on the level of activity of HIF1α. Thus, these cells represent a good human cell model for future investigations on islet cell transplantation analysis.

Key words: β-Cells; Hypoxia; Pseudoislets (PIs); HIF1α; Insulin secretion

Received January 6, 2016; final acceptance August 1, 2016. Online prepub date: August 12, 2016.
Address correspondence to Marie-José LecomteUnivercell-Biosolutions, Centre de recherche des Cordeliers, 15 rue de l’Ecole de Médecine, Paris, France. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it