Maha Azzam
Mansoura University, Egypt
Title: Insulin-producing cells from adult human bone marrow mesenchymal stem cells control chemically-induced diabetes in dogs
Biography
Biography: Maha Azzam
Abstract
Evidence was provided that human bone marrow-derived mesenchymal stem cells (HBM-MSCs) could be differentiated to form insulin- producing cells (IPCs). The efficacy of these cells to control diabetes in large animals was carried out to evaluate the sufficient number of cells needed/kg body weight and to determine the functional longevity in vivo. Ten male mongrel dogs weighting 15-20 kg were used in this study. Diabetes was chemically-induced in 7 dogs by a mixture of alloxan and streptozotocin. Three non-diabetic dogs served as normal controls. Differentiated HBM-MSCs (5 million /Kg) were encapsulated in Theracyte capsules and transplanted beneath the rectus sheath. Each dog received 2 capsules. One dog died 4 days postoperative from inhalation pneumonia. The remaining 6 dogs were followed up for 6-18 months. Four dogs became norm glycemic within 6- 8 weeks with normal glucose tolerance curves providing evidence that the transplanted cells were glucose-sensitive and insulin-responsive. In the remaining 2 dogs, fasting blood glucose was reduced but did not reach euglycemic levels. The sera of all transplanted dogs contained human insulin and c-peptide but negligible levels of canine insulin. When the HBM-MSCs- loaded capsules were removed, rapid return of diabetic state was noted. The harvested capsules were examined by immunofluorescence. IPCs were seen and co-expression of c- peptide was confirmed. Furthermore, all the pancreatic endocrine genes were expressed by the transplanted cells. Conclusions: This study provided evidences that Theracyte capsules could protect the xenogeneic HBM-MSCs from the host immune response. This is an important issue when clinical stem cell therapy is considered for definitive treatment for T1DM.