Intravenous vs intraperitoneal transplantation of umbilical cord mesenchymal stem cells from Wharton’s jelly in the treatment of streptozotocin-induced diabetic rats

El-Hossary, Nancy; Hassanein, Hamdy; El–Ghareeb, Abdel Wahab; Issa, Hisham

doi:10.1016/j.diabres.2016.09.008

Cited by 7 publications

(7 citation statements)

References 47 publications

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“…The i. p. cells transplantation approach has gained increasing interest in recent years, principally as local approach to treat peritoneal fibrosis or inflammatory or/and autoimmune diseases affecting visceral organs ( Bertram et al 1999 ; Li et al 2009 ; Wakabayashi et al 2014 ; El-Hossary et al 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, a study reported the successful attenuation of streptozotocin-induced diabetes via systemic transplantation of human UC-MSC, while in contrast no effectiveness was obtained through the i. p. transplantation route ( El-Hossary et al 2016 ). Contrary to these outcomes, our results suggest that the i. p. transplantation of heterologous UC-MSC is an effective transplantation approach for T1DM treatment.…”

Section: Discussionmentioning

confidence: 99%

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Umbilical cord mesenchymal stromal cells transplantation delays the onset of hyperglycemia in the RIP-B7.1 mouse model of experimental autoimmune diabetes through multiple immunosuppressive and anti-inflammatory responses

Lachaud

Cobo-Vuilleumier²,

Fuente-Martín³

et al. 2023

Front. Cell Dev. Biol.

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Type 1 diabetes mellitus (T1DM) is an autoimmune disorder specifically targeting pancreatic islet beta cells. Despite many efforts focused on identifying new therapies able to counteract this autoimmune attack and/or stimulate beta cells regeneration, TD1M remains without effective clinical treatments providing no clear advantages over the conventional treatment with insulin. We previously postulated that both the inflammatory and immune responses and beta cell survival/regeneration must be simultaneously targeted to blunt the progression of disease. Umbilical cord-derived mesenchymal stromal cells (UC-MSC) exhibit anti-inflammatory, trophic, immunomodulatory and regenerative properties and have shown some beneficial yet controversial effects in clinical trials for T1DM. In order to clarify conflicting results, we herein dissected the cellular and molecular events derived from UC-MSC intraperitoneal administration (i.p.) in the RIP-B7.1 mouse model of experimental autoimmune diabetes. Intraperitoneal (i.p.) transplantation of heterologous mouse UC-MSC delayed the onset of diabetes in RIP-B7.1 mice. Importantly, UC-MSC i. p. transplantation led to a strong peritoneal recruitment of myeloid-derived suppressor cells (MDSC) followed by multiple T-, B- and myeloid cells immunosuppressive responses in peritoneal fluid cells, spleen, pancreatic lymph nodes and the pancreas, which displayed significantly reduced insulitis and pancreatic infiltration of T and B Cells and pro-inflammatory macrophages. Altogether, these results suggest that UC-MSC i. p. transplantation can block or delay the development of hyperglycemia through suppression of inflammation and the immune attack.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Umbilical cord mesenchymal stromal cells transplantation delays the onset of hyperglycemia in the RIP-B7.1 mouse model of experimental autoimmune diabetes through multiple immunosuppressive and anti-inflammatory responses

Lachaud

Cobo-Vuilleumier²,

Fuente-Martín³

et al. 2023

Front. Cell Dev. Biol.

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“…Human umbilical cord Wharton jelly-derived MSCs (hUCMSCs) are adult stem cells capable of differentiating into several cell phenotypes. 12 Not only are hUCMSCs easy to obtain, but the cells also display the unique self-renewal, plastic adherence, large differentiation potential in vivo, and immunomodulatory properties that prevent tissue rejection. 12 A study conducted by Chao et al (2008) successfully originated islet-like clusters derived from MSCs from the Wharton jelly of the human umbilical cord for transplantation to control T1D.…”

Section: Umbilical Cord Tissue and Bloodmentioning

confidence: 99%

“…12 Not only are hUCMSCs easy to obtain, but the cells also display the unique self-renewal, plastic adherence, large differentiation potential in vivo, and immunomodulatory properties that prevent tissue rejection. 12 A study conducted by Chao et al (2008) successfully originated islet-like clusters derived from MSCs from the Wharton jelly of the human umbilical cord for transplantation to control T1D. Unfortunately, hUCMSCs have the tremendous practical burden of banking cord tissue, and the momentum to develop hUCMSC therapies has diminished because many current patients with T1D do not have the required stored tissue.…”

Section: Umbilical Cord Tissue and Bloodmentioning

confidence: 99%

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Current and Future Approaches to Stem Cell Treatment of Type I Diabetes

Yacoub

Webert

Lindberg

et al. 2018

Georgetown Medical Review

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This review analyzes the efficacy of current and previous stem cell therapies for type 1 diabetes (T1D) and suggests the most viable stem cell-based treatments for the future. T1D is an autoimmune disease in which the β cells of the pancreas are destroyed. Currently, the only insulin replacement therapy options for T1D include insulin injection (which requires daily dosing) or organ transplantation (which has donor limitations and requires immunosuppression). Both options decrease a patient's quality of life. After reviewing completed clinical trials using stem cell therapy, we found that the combination therapy of adipose-derived stem cells and hematopoietic stem cells offers the greatest benefit for generating insulin-producing cells and modulating the autoreactivity of the immune system. However, this therapy is limited in scope and requires immunosuppression. The most promising potential treatment is encapsulation (the enclosure of stem cell-derived β cells to prevent interactions with the immune system) because it can restore insulin production and does not require immunosuppression. Although encapsulation is in the early stages of development and has no completed clinical trials, it offers an ideal, long-term therapy option without compromising patients' quality of life and without requiring immunosuppression.

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MiR-375 inhibits the hepatocyte growth factor-elicited migration of mesenchymal stem cells by downregulating Akt signaling

Kang

et al. 2018

Cell Tissue Res

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The migration of mesenchymal stem cells (MSCs) is critical for their use in cell-based therapies. Accumulating evidence suggests that microRNAs are important regulators of MSC migration. Here, we report that the expression of miR-375 was downregulated in MSCs treated with hepatocyte growth factor (HGF), which strongly stimulates the migration of these cells. Overexpression of miR-375 decreased the transfilter migration and the migration velocity of MSCs triggered by HGF. In our efforts to determine the mechanism by which miR-375 affects MSC migration, we found that miR-375 significantly inhibited the activation of Akt by downregulating its phosphorylation at T308 and S473, but had no effect on the activity of mitogen-activated protein kinases. Further, we showed that 3'phosphoinositide-dependent protein kinase-1 (PDK1), an upstream kinase necessary for full activation of Akt, was negatively regulated by miR-375 at the protein level. Moreover, miR-375 suppressed the phosphorylation of focal adhesion kinase (FAK) and paxillin, two important regulators of focal adhesion (FA) assembly and turnover, and decreased the number of FAs at cell periphery. Taken together, our results demonstrate that miR-375 inhibits HGF-elicited migration of MSCs through downregulating the expression of PDK1 and suppressing the activation of Akt, as well as influencing the tyrosine phosphorylation of FAK and paxillin and FA periphery distribution.

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Intravenous vs intraperitoneal transplantation of umbilical cord mesenchymal stem cells from Wharton’s jelly in the treatment of streptozotocin-induced diabetic rats

Cited by 7 publications

References 47 publications

Umbilical cord mesenchymal stromal cells transplantation delays the onset of hyperglycemia in the RIP-B7.1 mouse model of experimental autoimmune diabetes through multiple immunosuppressive and anti-inflammatory responses

Umbilical cord mesenchymal stromal cells transplantation delays the onset of hyperglycemia in the RIP-B7.1 mouse model of experimental autoimmune diabetes through multiple immunosuppressive and anti-inflammatory responses

Current and Future Approaches to Stem Cell Treatment of Type I Diabetes

MiR-375 inhibits the hepatocyte growth factor-elicited migration of mesenchymal stem cells by downregulating Akt signaling

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