Oral Communications 6
13.6 - Co-infusion of Insulin-secreting adipose tissue derived mesenchymal stem cells and hematopoietic stem cells - novel approach to management of type 1 diabetes mellitus
Presenter: Umang, Thakkar, AHMEDABAD, India
Authors: Umang Thakkar1,2,3, Hargovind Trivedi1,2,3, Shruti Dave1,2,3, Aruna Vanikar1,2,3, Manish Rawal1,2,3
Co-infusion of Insulin-secreting adipose tissue derived mesenchymal stem cells and hematopoietic stem cells - novel approach to management of type 1 diabetes mellitus
Umang Thakkar1,2,3, Hargovind Trivedi1,2,3, Shruti Dave1,2,3, Aruna Vanikar1,2,3, Manish Rawal1,2,3
1Department of Stem Cell Therapy and Regenerative Medicine, G. R. Doshi and K. M. Mehta Institute Of Kidney Diseases & Research Centre (IKDRC)- Dr. H.L. Trivedi Institute Of Transplantation Sciences (ITS), AHMEDABAD, India; 2Department of Nephrology and Transplantation Medicine, G. R. Doshi and K. M. Mehta Institute Of Kidney Diseases & Research Centre (IKDRC)- Dr. H.L. Trivedi Institute Of Transplantation Sciences (ITS), AHMEDABAD, India; 3Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, G. R. Doshi and K. M. Mehta Institute Of Kidney Diseases & Research Centre (IKDRC)- Dr. H.L. Trivedi Institute Of Transplantation Sciences (ITS), AHMEDABAD, India
Introduction:Type 1 diabetes mellitus (T1DM) results from a cell-mediated autoimmune attack against pancreatic beta cells confirmed with positive antibodies against glutamic acid decarboxylase (GAD). Among them 30% of patients develop end-organ failure. Stem cell therapy (SCT) has promising results in regeneration of injured tissues/ cells as well as in correcting immune dysregulation. We present our experience of co-infusion of autologous and allogeneic adipose tissue derived insulin secreting mesenchymal stem cells (IS-AD-MSC) along with hematopoietic stem cells (HSC) in a cohort of patients with T1DM.
Material and methods: This was an Institutional Review Board approved prospective non-randomized open-labeled clinical trial after informed consent of 20 patients (15 males and 5 females) with T1DM for SCT. Their mean disease duration was 9 ± 5.51 years. Mean age was 19.95 ± 8.35 years with mean weight of 49.9 ±14 kg. Our study includes GAD antibody positive, T1DM patients with history of diabetic ketoacidosis. Associated findings were keratoconus, parathyroid adenoma producing hyperparathyroidism, attention deficit disorder, depression, mitral valve prolapse, nephritic syndrome and non-autoimmune hypothyroidism each in 1 patient and autoimmune thyroiditis was noted in 2 patients who were diagnosed as polyglandular autoimmune syndrome type-3 during the treatment. They were monitored for blood sugar levels, serum c-peptide, GAD antibodies and glycosylated hemoglobin (Hb1Ac) at 3 monthly intervals post-therapy. Patients/donors were subjected to adipose tissue resection for in vitro generation of IS-AD-MSC and bone marrow (BM) aspiration for generation of HSC. Generated SCs were infused in liver through portal circulation since liver is the most tolerogenic organ, in thymus to generate central tolerance and subcutaneous tissue of abdomen since that is the most immunologically privileged site. SC infusion was performed via femoral catheterization under local anesthesia. Exogenous insulin administration was made on sliding-scale with an objective of maintaining fasting blood sugar (FBS) <150 mg/dL and post-prandial blood sugar (PPBS) < 200 mg/dL. Associated findings were managed independently in all patients.
Results: Total mean quantum of SC infused was 99.5 ± 22.5 mL with mean nucleated cell count of 2.38 × 104/µL and mean CD34+ 0.57%. Mean CD45-/90+ and CD45-/73+ were 47.22% and 24.66% respectively. All the generated cells expressed transcription factors ISL-1, PAX-6 and IPF-1. No untoward effect of SCT was noted. Variable and sustained improvement in mean FBS, PPBS, HbA1C and serum C-peptide was noted in all patients over a mean follow-up of 43.94 ± 19.8 months. Mean GAD antibody has decreased from 525.15 to 120.15 after treatment. Mean insulin requirement decreased from 60.89 IU/day to 39.76 IU/day. There was no significant difference in acquiring insulinopenic stage between allogeneic and autologous infusion. There was absence of ketoacidotic episodes in all of them after SCT. All of them are feeling good with weight gain and improved energy levels.
Conclusion:Co-infusion of IS-AD-MSC with BM derived HSC offers a safe and viable therapy for T1DM.