Insulin-secreting adipose-derived mesenchymal stromal cells with bone marrow–derived hematopoietic stem cells from autologous and allogenic sources for type 1 diabetes mellitus

Thakkar, Umang G; Trivedi, Hargovind L; Vanikar, Aruna V; Dave, Shruti D

doi:10.1016/j.jcyt.2015.03.608

Cited by 116 publications

(74 citation statements)

References 20 publications

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“…First, the impact of immunomodulation by stem cells should be noted (13,36,37). In the present study, we could investigate T-cell activation and Treg-related cytokines before and after SCT.…”

Section: Discussionmentioning

confidence: 95%

“…Hu et al (29) reported metabolic improvements (fasting and postprandial glycemia, HbA 1c , fasting C-peptide) paralleled by reductions of exogenous insulin requirements following administration of UC-MSCs in newly diagnosed patients with T1D. Moreover, Thakkar et al (13) recently reported the safety and efficacy of coinfusion of insulin-secreting adiposederived MSCs and BM-HSCs in patients with T1D in which the use of autologous inoculum appeared to confer better long-term control of hyperglycemia compared with allogenic SCT.…”

Section: Discussionmentioning

confidence: 99%

“…Urbán et al (12) showed that transplantation of BM cells (BMCs) and MSCs in sublethally irradiated diabetic mice improved glycemic and serum insulin levels along with tissue regeneration and repair; in their study, combined BMC and MSC infusion appeared to be synergistic. Recently, Thakkar et al (13) reported that coinfusion of insulinsecreting adipose-derived MSCs and BM-HSCs is a clinically safe and viable treatment option for T1D.…”

mentioning

confidence: 99%

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Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion

Cai

et al. 2015

Diabetes Care

142

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OBJECTIVETo determine the safety and effects on insulin secretion of umbilical cord (UC) mesenchymal stromal cells (MSCs) plus autologous bone marrow mononuclear cell (aBM-MNC) stem cell transplantation (SCT) without immunotherapy in established type 1 diabetes (T1D). RESEARCH DESIGN AND METHODSBetween January 2009 and December 2010, 42 patients with T1D were randomized (n = 21/group) to either SCT (1.1 3 10 6 /kg UC-MSC, 106.8 3 10 6 /kg aBM-MNC through supraselective pancreatic artery cannulation) or standard care (control). Patients were followed for 1 year at 3-month intervals. The primary end point was C-peptide area under the curve (AUC C-Pep ) during an oral glucose tolerance test at 1 year. Additional end points were safety and tolerability of the procedure, metabolic control, and quality of life. RESULTSThe treatment was well tolerated. At 1 year, metabolic measures improved in treated patients: AUC C-Pep increased 105.7% (6.6 6 6.1 to 13.6 6 8.1 pmol/mL/180 min, P = 0.00012) in 20 of 21 responders, whereas it decreased 7.7% in control subjects (8.4 6 6.8 to 7.7 6 4.5 pmol/mL/180 min, P = 0.013 vs. SCT); insulin area under the curve increased 49.3% (1,477.8 6 1,012.8 to 2,205.5 6 1,194.0 mmol/mL/180 min, P = 0.01), whereas it decreased 5.7% in control subjects (1,517.7 6 630.2 to 1,431.7 6 441.6 mmol/mL/180 min, P = 0.027 vs. SCT). HbA 1c decreased 12.6% (8.6 6 0.81% [70.0 6 7.1 mmol/mol] to 7.5 6 1.0% [58.0 6 8.6 mmol/mol], P < 0.01) in the treated group, whereas it increased 1.2% in the control group (8.7 6 0.9% [72.0 6 7.5 mmol/mol] to 8.8 6 0.9% [73 6 7.5 mmol/mol], P < 0.01 vs. SCT). Fasting glycemia decreased 24.4% (200.0 6 51.1 to 151.2 6 22.1 mg/dL, P < 0.002) and 4.3% in control subjects (192.4 6 35.3 to 184.2 6 34.3 mg/dL, P < 0.042). Daily insulin requirements decreased 29.2% in only the treated group (0.9 6 0.2 to 0.6 6 0.2 IU/day/kg, P = 0.001), with no change found in control subjects (0.9 6 0.2 to 0.9 6 0.2 IU/day/kg, P < 0.01 vs. SCT). CONCLUSIONSTransplantation of UC-MSC and aBM-MNC was safe and associated with moderate improvement of metabolic measures in patients with established T1D.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion

Cai

et al. 2015

Diabetes Care

142

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“…Using different inducers and methods such as dexamethasone, vitamin C, vitamin D, BMPs, TGF-β, FGF, or insulin, can induce MSCs to differentiate into different lineages such as osteoblasts, chondrocytes, fibroblasts, myoblasts and so on (9,(17)(18)(19)(20)(21)(22). The direction has been set but differentiated cells can reverse the differentiation induced under certain conditions.…”

Section: Discussionmentioning

confidence: 99%

BMP7‑overexpressing bone marrow‑derived mesenchymal stem cells (BMSCs) are more effective than wild‑type BMSCs in healing fractures

Xu¹,

Zhou

Guo³

et al. 2018

Exp Ther Med

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Abstract. Bone fractures are a worldwide public health concern. Previous studies have demonstrated that bone morphogenetic protein-7 (BMP7) gene transfer or mesenchymal stem cells (MSCs) transplantation may be a promising novel therapeutic approach. Therefore, the aim of the present study was to observe the effect of bone BMP7 transfer to MSCs on fracture healing. Bone marrow-derived MSCs (BMSCs) from New Zealand white rabbits were isolated and identified using flow cytometry. A recombinant BMP7 overexpressing adenovirus vector (Adv) was constructed and transfected into BMSCs. The expression of BMP7 was detected by reverse transcription-polymerase chain reaction, immunofluorescence and western blotting. The present study additionally investigated the effect of BMP7 on the differentiation capacity of BMSCs. Finally, tissue-engineered bone was created with support material to verify the effect of BMP7-BMSCs on fracture healing. The results demonstrated that the expression of BMP7 was increased at the mRNA and protein levels in BMSCs following transfection with BMP7 overexpressing Adv. The results additionally demonstrated that the expression of BMP7 enhanced the differentiation capacity of bone marrow mesenchymal stem cells and had a promotional effect on fracture healing. Overall, these data suggest that Adv-BMP7 is useful for introducing foreign genes into BMSCs and will be a powerful gene therapy tool for bone regeneration and other tissue engineering applications in the future.

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“…(Vanikar et al 2010; Thakkar et al 2015). Autologous transplantation via the intra-pancreatic route tended to have an improved C-peptide and postprandial glucose at 15–24 months when compared to allogenic transplantation.…”

Section: Mesenchymal Stem Cells To Treat Diabetesmentioning

confidence: 99%

Therapeutic potential of mesenchymal stem cells for diabetes

Moreira

Kahlenberg

Hornsby

2017

Journal of Molecular Endocrinology

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Mesenchymal stem cells (MSCs) are self-renewing multipotent cells that have the capacity to secrete multiple biologic factors that can restore and repair injured tissues. Preclinical and clinical evidence have substantiated the therapeutic benefit of MSCs in various medical conditions. Currently, MSCs are the most commonly used cell-based therapy in clinical trials because of their regenerative effects, ease of isolation, and low immunogenicity. Experimental and clinical studies have provided promising results using MSCs to treat diabetes. This review will summarize the role of MSCs on tissue repair, provide emerging strategies to improve MSC function, and describe how these processes translate to clinical treatments for diabetes.

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Insulin-secreting adipose-derived mesenchymal stromal cells with bone marrow–derived hematopoietic stem cells from autologous and allogenic sources for type 1 diabetes mellitus

Cited by 116 publications

References 20 publications

Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion

Umbilical Cord Mesenchymal Stromal Cell With Autologous Bone Marrow Cell Transplantation in Established Type 1 Diabetes: A Pilot Randomized Controlled Open-Label Clinical Study to Assess Safety and Impact on Insulin Secretion

BMP7‑overexpressing bone marrow‑derived mesenchymal stem cells (BMSCs) are more effective than wild‑type BMSCs in healing fractures

Therapeutic potential of mesenchymal stem cells for diabetes

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