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Novel therapy for insulin-dependent diabetes mellitus: infusion of in vitro-generated insulin-secreting cells

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Abstract

Insulin-dependent diabetes mellitus (IDDM) is a metabolic disease usually resulting from autoimmune-mediated β-cell destruction requiring lifetime exogenous insulin replacement. Mesenchymal stem cells (MSC) hold promising therapy. We present our experience of treating IDDM with co-infusion of in vitro autologous adipose tissue-derived MSC-differentiated insulin-secreting cells (ISC) with hematopoietic stem cells (HSC). This was an Institutional Review Board approved prospective non-randomized open-labeled clinical trial after informed consent from ten patients. ISC were differentiated from autologous adipose tissue-derived MSC and were infused with bone marrow-derived HSC in portal, thymic circulation by mini-laparotomy and in subcutaneous circulation. Patients were monitored for blood sugar levels, serum C-peptide levels, glycosylated hemoglobin (Hb1Ac) and glutamic acid decarboxylase (GAD) antibodies. Insulin administration was made on sliding scale with an objective of maintaining FBS < 150 mg/dL and PPBS around 200 mg/dL. Mean 3.34 mL cell inoculums with 5.25 × 104 cells/μL were infused. No untoward effects were observed. Over a mean follow-up of 31.71 months, mean serum C-peptide of 0.22 ng/mL before infusion had sustained rise of 0.92 ng/mL with decreased exogenous insulin requirement from 63.9 international units (IU)/day to 38.6 IU/day. Improvement in mean Hb1Ac was observed from 10.99 to 6.72 %. Mean GAD antibodies were positive in all patients with mean of 331.10 IU/mL, which decreased to mean of 123 IU/mL. Co-infusion of autologous ISC with HSC represents a viable novel therapeutic option for IDDM.

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Abbreviations

BM:

Bone marrow

CBM:

Cultured bone marrow

DKA:

Diabetic ketoacidosis

FBS:

Fasting blood sugar levels

GAD:

Glutamic acid decarboxylase

Hb1Ac:

Glycosylated hemoglobin

HSC:

Hematopoietic stem cells

ISC:

Insulin-secreting cells

MSC:

Mesenchymal stem cells

PPBS:

Postprandial blood sugar level

IDDM:

Insulin-dependent diabetes mellitus

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Acknowledgments

The authors thank the staff and technicians of IKDRC-ITS, India, for all the technical help. The authors also thank Shobhana Sengunthar for providing statistical analysis.

Conflict of interest

None.

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Authors and Affiliations

  1. Stem Cell Lab, Transplantation Biology Research Centre, Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, G. R. Doshi and K. M. Mehta Institute of Kidney Diseases and Research Centre (IKDRC)-Dr. H.L. Trivedi Institute of Transplantation Sciences (ITS), Civil Hospital Campus, Asarwa, Ahmedabad, 380016, Gujarat, India

    S. D. Dave & A. V. Vanikar

  2. Department of Nephrology and Transplantation Medicine, IKDRC-ITS, Ahmedabad, Gujarat, India

    H. L. Trivedi

  3. Department of Stem Cell Therapy and Regenerative Medicine, IKDRC-ITS, Ahmedabad, Gujarat, India

    H. L. Trivedi & U. G. Thakkar

  4. Department of Surgery, Banaras Hindu University, Varanasi, Uttar Pradesh, India

    S. C. Gopal

  5. Department of Transfusion Medicine, King George Medical University, Lucknow, Uttar Pradesh, India

    T. Chandra

Authors
  1. S. D. Dave
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  2. A. V. Vanikar
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  3. H. L. Trivedi
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  4. U. G. Thakkar
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  5. S. C. Gopal
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  6. T. Chandra
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Correspondence to S. D. Dave.

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Dave, S.D., Vanikar, A.V., Trivedi, H.L. et al. Novel therapy for insulin-dependent diabetes mellitus: infusion of in vitro-generated insulin-secreting cells. Clin Exp Med 15, 41–45 (2015). https://doi.org/10.1007/s10238-013-0266-1

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  • DOI: https://doi.org/10.1007/s10238-013-0266-1

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