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Table 1 Summary of the major MSC-derived studies in pre-clinical animal models of T1D

From: CRISPR-targeted genome editing of mesenchymal stem cell-derived therapies for type 1 diabetes: a path to clinical success?

Treatment type

Intervention

Outcomes

Fresh/frozen

Reference

Immunomodulation

Mice received 1 × 106 AD-MSCs by i.p. injection

Reversal of hyperglycaemia characterised by increased serum insulin, amylin, and GLP-1 levels. Downregulation of the CD4+ Th1-based immune response and expansion of Tregs in the pancreatic lymph nodes.

Fresh

[13]

Mice received 1 × 105 MSCs either i.p. or i.v.

Reduced infiltration of T cells to pancreatic islets associated with preferential migration of MSCs to pancreatic lymph nodes.

Fresh

[14]

Mice received 0.5 × 106 MSCs administered systemically

Reduced blood glucose levels and an increase in morphologically normal pancreatic islets.

Fresh

[16]

Rats received 2–4 × 106 MSCs via tail vein injection

Enhanced insulin secretion and sustained normoglycaemia. Islets from treated rats co-expressed high levels of Pdx-1 and insulin.

Fresh

[17]

Mice received a co-transplantation of primary hBMSCs and human islets at serial ratios under the kidney capsule

Good blood glucose control and increased levels of serum insulin and C-peptide when islets were co-transplanted with hBMSCs. hBMSCs also increased the percentage of Tregs and prevented cytokine-induced loss-of-function of transplanted islets.

Fresh

[19]

Mice received 5 × 105 MSCs injected i.v. once a week for 4 weeks

BALB/c-MSC trafficked to the pancreatic lymph nodes of treated animals. Administration of BALB/c-MSC temporarily resulted in reversal of hyperglycaemia in 90% of treated animals.

Fresh

[30]

IPC differentiation

Chemical differentiation

BMSCs formed islet-like clusters containing IPCs that expressed multiple pancreatic genes. The clusters released insulin in a glucose-dependent manner and ameliorated diabetes in STZ-treated nude mice.

Fresh

[6]

Chemical differentiation

BMSCs differentiated into IPCs and acquired islet-like architecture after transplantation, developed an endocrine gene expression profile and demonstrated glucose-responsive insulin secretion. Subcapsular renal transplantation of these aggregates lowered circulating blood glucose levels.

Fresh

[8]

Chemical differentiation

Differentiated BMSCs expressed multiple pancreatic genes and exhibited glucose-responsive insulin secretion. Transplantation into STZ-diabetic mice imparted reversal of hyperglycaemia and an improved IPGTT.

Fresh

[9]

Chemical differentiation

Differentiation cells expressed pancreatic genes and displayed glucose-responsive insulin secretion. Transplantation of differentiated cells into diabetic rats reduced blood sugar levels.

Fresh

[33]

Viral-mediated differentiation

Differentiated cells expressed all four islet hormones and demonstrated glucose-responsive insulin secretion. Cell transplantation into STZ-diabetic immune-deficient mice resulted in further differentiation, including induction of NeuroD1 and reduction of hyperglycaemia.

Fresh

[11]

Viral-mediated differentiation

hMSCs differentiated into IPCs that expressed multiple islet genes and released insulin/C-peptide in a weak glucose-responsive manner. Upon transplantation into STZ-diabetic mice, normoglycaemia was obtained within 2 weeks and maintained for at least 42 days.

Fresh

[12]

Viral-mediated differentiation

Differentiated AD-MSC expressed some islet genes and secreted increasing amounts of insulin in response to increasing concentrations of glucose. Transplantation in STZ-diabetic rats resulted in lowered blood glucose and higher glucose tolerance.

Fresh

[36]

Viral-mediated differentiation

Expression of Pdx1 in AD-MSCs did not induce the pancreatic phenotype in vitro. Upon transplantation, the cells engrafted in the pancreas, wherein they expressed insulin and C-peptide, significantly decreased blood glucose levels, and increased survival.

Fresh

[37]

Viral-mediated differentiation

Body weight in diabetic mice that received GFP-mMSCs expressing the human insulin gene was increased by 6% within 6 weeks after treatment.

Fresh

[39]

  1. AD-MSC adipose-derived mesenchymal stem cell, BMSC bone marrow mesenchymal stem cell, CD cluster of differentiation, GFP green fluorescent protein, GLP-1 glucagon-like peptide 1, hBMSC human bone marrow mesenchymal stem cell, i.p. intraperitoneal, IPC insulin producing cell, IPGTT intraperitoneal glucose tolerance test, i.v. intravenous, MSC mesenchymal stem cell, Pdx-1 pancreatic and duodenal homeobox 1, STZ streptozotocin, T regs regulatory T cells, mMSC murine mesenchymal stem cell, BALB/c-MSC Bagg Albino mesencymal stem cells