Mesenchymal stroma cells improve hyperglycemia and insulin deficiency in the diabetic porcine pancreatic microenvironment

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

doi:10.1080/14653240802461924

Cited by 28 publications

(18 citation statements)

References 24 publications

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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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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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“…islets in the pancreas and reversal of hyperglycemia after MSCs were transplanted into the pancreatic subcapsular region, 40 the therapeutic effects in our study in the PST groups was much better than those in the TVT groups. This distinction may be explained by the different quantity of MSCs residing in the pancreas.…”

Section: Discussionmentioning

confidence: 68%

Immunogenicity of allogeneic mesenchymal stem cells transplanted via different routes in diabetic rats

Zhang

Yang

et al. 2014

Cell Mol Immunol

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Due to their hypoimmunogenicity and unique immunosuppressive properties, mesenchymal stem cells (MSCs) are considered one of the most promising adult stem cell types for cell therapy. Although many studies have shown that MSCs exert therapeutic effects on several acute and subacute conditions, their long-term effects are not confirmed in chronic diseases. Immunogenicity is a major limitation for cell replacement therapy, and it is not well understood in vivo. We evaluated the immunogenicity of allogeneic MSCs in vivo by transplanting MSCs into normal and diabetic rats via the tail vein or pancreas and found that MSCs exhibited low immunogenicity in normal recipients and even exerted some immunosuppressive effects in diabetic rats during the initial phase. However, during the later stage in the pancreas group, MSCs expressed insulin and MHC II, eliciting a strong immune response in the pancreas. Simultaneously, the peripheral blood mononuclear cells in the recipients in the pancreas group were activated, and alloantibodies developed in vivo. Conversely, in the tail vein group, MSCs remained immunoprivileged and displayed immunosuppressive effects in vivo. These data indicate that different transplanting routes and microenvironments can lead to divergent immunogenicity of MSCs.

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“…The feature of self-origin and readily ex vivo expansion renders these stem cells a practical approach to avoiding the use of antirejection drugs. A number of studies demonstrated that bone marrow-derived stem cells could be differentiated into β-cell-like insulin-producing cells both in vitro and in vivo (Chen et al 2004;Chang et al 2008). The differentiated cells possessed the ability to control blood glucose level in streptozotocin (STZ)-induced diabetic animals.…”

Section: Autologous Adult Stem Cell-derived β-Cell Replacementmentioning

confidence: 98%

Do immunotherapy and ß cell replacement play a synergistic role in the treatment of type 1 diabetes?

Li¹,

Warnock²,

Tu³

et al. 2009

Life Sciences

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Mesenchymal stroma cells improve hyperglycemia and insulin deficiency in the diabetic porcine pancreatic microenvironment

Cited by 28 publications

References 24 publications

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

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

Immunogenicity of allogeneic mesenchymal stem cells transplanted via different routes in diabetic rats

Do immunotherapy and ß cell replacement play a synergistic role in the treatment of type 1 diabetes?

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