Co-infusion of insulin-secreting adipose tissue-derived mesenchymal stem cells and hematopoietic stem cells: novel approach to management of type 1 diabetes mellitus

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• 作者：U. G. Thakkar ; H. L. Trivedi ; A. V. Vanikar…
• 关键词：Type 1 diabetes mellitus ; Insulin requirement ; C ; peptide ; Glycosylated hemoglobin ; Stem cell therapy ; Mesenchymal stem cells ; Hematopoietic stem cells
• 刊名：International Journal of Diabetes in Developing Countries
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：36
• 期：4
• 页码：426-432
• 全文大小：
• 刊物主题：Medicine/Public Health, general; General Practice / Family Medicine; Health Administration; Diabetes;
• 出版者：Springer India
• ISSN：1998-3832
• 卷排序：36

文摘

Stem cell therapy (SCT) has promising results in regeneration of injured tissues/cells as well as correcting immune dysregulation. We present our experience of co-infusion of human adipose tissue-derived insulin-secreting mesenchymal stem cells (IS-AD-MSC) along with bone marrow-derived hematopoietic stem cells (BM-HSC) in type 1 diabetes mellitus (T1DM). 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, with mean disease duration of 9 ± 5.51 years. Their mean age and weight were 19.95 ± 8.35 years and 49.9 ± 14 kg, respectively. Our study includes T1DM with positive for glutamic acid decarboxylase (GAD) antibody and history of diabetic ketoacidosis (DKA). Generated IS-AD-MSC and BM-HSC were infused via femoral catheterization under local anesthesia into portal + thymic circulation and subcutaneous tissue with conditioning of injection rabbit anti-thymocyte globulin and Bortezomib. Patients were monitored for blood sugar, serum C-peptide, GAD antibodies, and glycosylated hemoglobin (Hb1Ac) at three monthly intervals post-therapy. Mean SC quantum infused 99.45 ± 22.5 mL, with mean 2.38 ± 0.78 × 104 ISC/μL, mean CD34+ 0.57 %, and mean CD45-/90+ and CD45-/73+ were 47.22 and 24.66 %, respectively. Generated ISCs expressed transcription factors ISL-1, PAX-6, and IPF-1. Variable and sustained improvement in mean FBS, PPBS, HbA1c, and serum C-peptide was noted over a mean follow-up of 43.94 ± 19.8 months with mean reduction of GAD antibody from 525.15 to 120.15 IU/mL. Mean insulin requirement decreased from 60.89 to 39.76 IU/day. There was absence of DKA after SCT. No untoward effect/morbidity/mortality was recorded from SCT. Co-infusion of IS-AD-MSC with BM-HSC offers a safe and viable therapy for T1DM.