Mesenchymal Stem Cells Contribute to Insulin-Producing Cells Upon Microenvironmental Manipulation In Vitro

Chang, Caihong; Deliang, Niu; Zhou, Haixia; Li, F.; Gong, Feili

doi:10.1016/j.transproceed.2007.09.026

Cited by 27 publications

(11 citation statements)

References 15 publications

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“…To construct a stimulated pancreatic microenvironment, rabbit pancreatic pieces were delivered into niobium‐coated Dynamatrix, upon which soluble cytokine exchange and direct cell‐to‐cell contact between BM‐MSCs and pancreatic cells could occur. BM‐MSCs cultured on the constructed microenvironment (with experimental diabetic rabbit serum) differentiated into islet‐like cells (Chang et al , 2007).…”

Section: Discussionmentioning

confidence: 99%

Bone marrow-derived mesenchymal stem cells co-cultured with pancreatic islets display β cell plasticity

Karaöz

Ayhan

Okçu

et al. 2010

J Tissue Eng Regen Med

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The direct co-culturing effect of rat bone-marrow-derived mesenchymal stem cells (rBM-MSCs) on the pancreatic-islets (PIs) was studied to obtain functional islet cells. MSCs were isolated from rat bone marrow and cultivated under standard conditions. Following their characterization, the rBM-MSCs were directly (with cell-islet contact) co-cultured with recovered PIs together with the single cell cultures of those cell cultures as a control. The effect of direct co-cultures of rBM-MSCs with the PIs of normal rats was investigated using immunophenotypical and functional methods. The change in the amount of insulin secretion was evaluated as an indicator for differentiation of rBM-MSCs. One approache for in vitro differentiation to achieve reprogramming for differentiation into suitable cell types by changing the microenvironment of the cells to provide signals that might activate metabolic pathways is to use co-cultures with the microenvironment of the specific cells of the desired cell type, tissue/organ extracts, extracellular matrix compounds or biologically absorbable materials. Differentiated rBM-MSCs were found to be immunopositive for the specific insulin-producing cell marker, insulin, but not in undifferentiated rBM-MSCs. The functionality tests by ELISA confirmed that insulin secretion of co-cultured MSCs with islets was higher than that of islets. These evidences indicated that PIs could be regarded as critical components of the stem cell niche, such that MSCs can be differentiated into insulin-producing cells (IPCs). Moreover, direct cell-to-cell contact might provide additional and independent support. This approach would circumvent the need for PI-stem cell co-culture and could potentially facilitate the production of functional IPCs for future clinical applications.

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Section: Discussionmentioning

confidence: 99%

Bone marrow-derived mesenchymal stem cells co-cultured with pancreatic islets display β cell plasticity

Karaöz

Ayhan

Okçu

et al. 2010

J Tissue Eng Regen Med

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“…In another study, the same group reported that mesenchymal stromal cells (MStC) could improve hyperglycemia and insulin production in a diabetic microenvironment [21]. They transplanted male porcine bone marrow-derived EGFPexpressing MStCs directly into female diabetic porcine pancreas by multi-point injection, and observed that MStCs could adopt beta-cell fate [22] in the diabetic microenvironmental niche, and restore normoglycemia without obvious immune rejections.…”

Section: Abbreviationsmentioning

confidence: 99%

Mesenchymal Stem Cells Derived from Bone Marrow of Diabetic Patients Portrait Unique Markers Influenced by the Diabetic Microenvironment

Phadnis¹,

Ghaskadbi²,

Hardikar³

et al. 2009

Rev Diabet Stud

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■ AbstractCellular microenvironment is known to play a critical role in the maintenance of human bone marrow-derived mesenchymal stem cells (BM-MSCs). It was uncertain whether BM-MSCs obtained from a 'diabetic milieu' (dBM-MSCs) offer the same regenerative potential as those obtained from healthy (non-diabetic) individuals (hBM-MSCs). To investigate the effect of diabetic microenvironment on human BMMSCs, we isolated and characterized these cells from diabetic patients (dBM-MSCs). We found that dBM-MSCs expressed mesenchymal markers such as vimentin, smooth muscle actin, nestin, fibronectin, CD29, CD44, CD73, CD90, and CD105. These cells also exhibited multilineage differentiation potential, as evident from the generation of adipocytes, osteocytes, and chondrocytes when exposed to lineage specific differentiation media. Although the cells were similar to hBM-MSCs, 6% (3/54) of dBM-MSCs expressed proinsulin/C-peptide. Emanating from the diabetic microenvironmental milieu, we analyzed whether in vitro reprogramming could afford the maturation of the islet-like clusters (ICAs) derived from dBM-MSCs. Upon mimicking the diabetic hyperglycemic niche and the supplementation of fetal pancreatic extract, to differentiate dBM-MSCs into pancreatic lineage in vitro, we observed rapid differentiation and maturation of dBM-MSCs into islet-like cell aggregates. Thus, our study demonstrated that diabetic hyperglycemic microenvironmental milieu plays a major role in inducing the differentiation of human BM-MSCs in vivo and in vitro.

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“…Whereas the capacity to differentiate into osteocytes, adipocytes, and chondrocytes are defining features of MSCs in vitro, more potent transdifferentiation has been described. MSCs can be driven to differentiate into myocytes, endothelium, cardiomyocytes, fibroblasts, neural cells, and possibly hepatocytes, epithelium or even insulin producing cells, depending on the stimuli [27][28][29][30][31][32][33][34][35]. This multipotentiality combined with the ease of culture and expansion, have led to MSCs becoming a lead therapeutic in the race for cell based regenerative therapies [6,36].…”

Section: Tissue Repair and Regenerationmentioning

confidence: 99%

Mesenchymal Stromal Cells; Role in Tissue Repair, Drug Discovery and Immune Modulation

English¹,

Mahon²,

Wood³

2013

CDD

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Mesenchymal stromal cells (MSCs) participate in repair of damaged tissues, possess the potential to serve as a useful tool in the drug discovery field and exert immunosuppressive effects as demonstrated by their ability to modulate the immune response. Herein, the roles played by MSC differentiation and/or production of trophic factors involved in tissue repair are discussed. MSCs offer the opportunity to probe targets that conventional or differentiated cell lines do not express; thus providing a more refined system that allows identification of novel therapeutics. However, there are difficulties associated with drug discovery assays to which MSCs are not exempt. The immunosuppressive potential of MSCs has already been utilised in clinical trials where MSCs have been used to treat patients with graft-versus-host disease (GvHD) and autoimmune diseases. Another possible therapeutic application of MSCs lies in the field of transplantation tolerance. Although the capacity of MSCs to modulate immune responses has received much attention, the role of MSCs in transplantation tolerance is as yet unclear. In this review, we discuss the evidence for MSC induction of a state of tolerance in the transplantation setting.

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Mesenchymal Stem Cells Contribute to Insulin-Producing Cells Upon Microenvironmental Manipulation In Vitro

Cited by 27 publications

References 15 publications

Bone marrow-derived mesenchymal stem cells co-cultured with pancreatic islets display β cell plasticity

Bone marrow-derived mesenchymal stem cells co-cultured with pancreatic islets display β cell plasticity

Mesenchymal Stem Cells Derived from Bone Marrow of Diabetic Patients Portrait Unique Markers Influenced by the Diabetic Microenvironment

Mesenchymal Stromal Cells; Role in Tissue Repair, Drug Discovery and Immune Modulation

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