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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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Abstract

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.

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Acknowledgments

The authors are thankful to CN Patel for his help in media preparation for stem cell generation in lab and to JV Patel, BN Patel, JM Chudasma, HS Patel, and PN Bhavsar for carrying out all the laboratory tests including flow cytometry analysis of this patient. We are also thankful to our librarian Jyotsana Suthar for literature search.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Regenerative Medicine and Stem Cell Therapy, G.R. Doshi and K.M. Mehta Institute of Kidney Diseases & Research Centre (IKDRC) - Dr. H.L. Trivedi Institute of Transplantation Sciences (ITS), Ahmedabad, Gujarat, India

    U. G. Thakkar, H. L. Trivedi, A. V. Vanikar & S. D. Dave

  2. Department 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, Gujarat, India

    A. V. Vanikar

  3. Department 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, Gujarat, India

    H. L. Trivedi

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  1. U. G. Thakkar
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  2. H. L. Trivedi
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  4. S. D. Dave
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Correspondence to U. G. Thakkar.

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Thakkar, U.G., Trivedi, H.L., Vanikar, A.V. et al. Co-infusion of insulin-secreting adipose tissue-derived mesenchymal stem cells and hematopoietic stem cells: novel approach to management of type 1 diabetes mellitus. Int J Diabetes Dev Ctries 36, 426–432 (2016). https://doi.org/10.1007/s13410-015-0409-x

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  • DOI: https://doi.org/10.1007/s13410-015-0409-x

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