Mesenchymal Stem Cell and Islet Co-Transplantation Promotes Graft Revascularization and Function

Ito, Taihei; Itakura, Susumu; Todorov, Ivan; Rawson, Jeffrey; Asari, Sadaki; Shintaku, Jonathan; Nair, Indu; Ferreri, Kevin; Kandeel, Fouad; Mullen, Yoko

doi:10.1097/tp.0b013e3181db09c4

Cited by 238 publications

(234 citation statements)

References 30 publications

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“…Compared with previous studies using immunodeficient animals [52,54], the duration of insulin independence in humanized mice was significantly reduced [79], suggesting the existence of immune rejection. However, the introduction of human immunity also led to GvHD, a fetal disease characterized by the attack to the recipient's major organs by the infused xenogeneic immunocytes.…”

Section: Introductioncontrasting

confidence: 73%

“…Other studies suggested that BMSCs may also differentiate into endothelial cells and directly assist the neo-vessel formation [53]. Silva et al reported the transdifferentiation of BMSCs into an endothelial phenotype in a canine ischemia model, which is supported by the report from Ito et al that BMSCs directly differentiate into a van-willebrand-factor-positive vascular endothelial cell type to improve the islet graft morphology and function [54]. However, these results should be explained cautiously because the new-formed vessels may arise from native BMSCs instead of infused BMSCs.…”

Section: Bmscs Support Islet Functionsupporting

confidence: 66%

“…There are two hypotheses: 1) through the secretion of immunosuppressive cytokines, such as IL-10 and TGFβ [130]; and 2) through cell surface molecules of BMSCs to inhibit T cell activity and proliferation [71]. Previous reports showed that the co-transplantation of islets with primary BMSCs prevented the allogeneic rejection and helped engraftment of islets, but one common feature in all these studies was that the BMSCs were incompetent to reverse the blood glucose levels of recipients in the acute stage (<3 weeks) after transplantation, suggesting the slow engraftment of transplanted islets [43,54,116]. To make the situation even worse, the hyperglycemia caused by slow engraftment in turn accelerated the apoptotic islet cell death [95].…”

Section: Discussionmentioning

confidence: 99%

“…However, it should be noted that BMSCs alone, through systemic administration or local transplantation, were less competent to prevent the islet loss immediately after transplantation, which accounts for more than 70% of islet loss in the first week after transplantation [95,96]. This phenomenon probably explains the inadequate control of the blood glucose level in the early stage (< 3 weeks) after transplantation in most islet/MSC co-transplantation studies [54,116]. Because traditional gene transfer into human islets is less efficient and time consuming and BMSC mediated cell therapy is less competent to prevent the acute graft loss, we planned to utilize BMSC mediated gene therapy in this study.…”

Section: Introductionmentioning

confidence: 95%

“…In vitro expanded BMSCs co-infused into liver. Reduce islet number needed for reversal of diabetes promote revascularization [54]. Rat.…”

Section: Isletmentioning

confidence: 99%

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Gene Therapy and Stem Cell Therapy to Improve the Outcome of Human Islet Transplantation

Wu¹

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revised all my manuscripts and gave me the courage and the skills to write and present as a non-native English speaker.I must acknowledge as well the many friends, colleagues, students, teachers, and other librarians who assisted, advised, and supported my research and writing efforts over the years. Especially, I need to express my gratitude and deep appreciation to my wife Chengcheng Liu whose understanding, wisdom, and sense of humor have supported, enlightened, and entertained me over many years. She has consistently helped me keep perspective on what is important in life and shown me how to deal with reality.

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Section: Introductioncontrasting

confidence: 73%

Section: Bmscs Support Islet Functionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

“…In vitro expanded BMSCs co-infused into liver. Reduce islet number needed for reversal of diabetes promote revascularization [54]. Rat.…”

Section: Isletmentioning

confidence: 99%

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Gene Therapy and Stem Cell Therapy to Improve the Outcome of Human Islet Transplantation

Wu¹

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The use of mesenchymal stromal cells in solid organ transplantation

Delens

Jouret

Detry

et al. 2016

The Biology and Therapeutic Application of Mesenchymal Cells

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MRI/SPECT/Fluorescent Tri‐Modal Probe for Evaluating the Homing and Therapeutic Efficacy of Transplanted Mesenchymal Stem Cells in a Rat Ischemic Stroke Model

Tang

Zhang

Wang

et al. 2014

Adv Funct Materials

104

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Quantitatively tracking engraftment of intracerebrally or intravenously transplanted stem cells and evaluating their concomitant therapeutic efficacy for stroke has been a challenge in the field of stem cell therapy. In this study, first, an MRI/SPECT/fluorescent tri-modal probe (125I-fSiO4@SPIOs) is synthesized for quantitatively tracking mesenchymal stem cells (MSCs) transplanted intracerebrally or intravenously into stroke rats, and then the therapeutic efficacy of MSCs delivered by both routes and the possible mechanism of the therapy are evaluated. It is demonstrated that (125)I-fSiO4@SPIOs have high efficiency for labeling MSCs without affecting their viability, differentiation, and proliferation capacity, and found that 35% of intracerebrally injected MSCs migrate along the corpus callosum to the lesion area, while 90% of intravenously injected MSCs remain trapped in the lung at 14 days after MSC transplantation. However, neurobehavioral outcomes are significantly improved in both transplantation groups, which are accompanied by increases of vascular endothelial growth factor, basic fibroblast growth factor, and tissue inhibitor of metalloproteinases-3 in blood, lung, and brain tissue (p < 0.05). The study demonstrates that 125I-fSiO4@SPIOs are robust probe for long-term tracking of MSCs in the treatment of ischemic brain and MSCs delivered via both routes improve neurobehavioral outcomes in ischemic rats.

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Mesenchymal Stem Cell and Islet Co-Transplantation Promotes Graft Revascularization and Function

Abstract: Our results demonstrate the improvement of islet graft morphology and function by co-transplantation with MSCs. This improvement is attributable, at least in part, to the promotion of graft revascularization mediated by MSCs.

Cited by 238 publications

References 30 publications

Gene Therapy and Stem Cell Therapy to Improve the Outcome of Human Islet Transplantation

Gene Therapy and Stem Cell Therapy to Improve the Outcome of Human Islet Transplantation

The use of mesenchymal stromal cells in solid organ transplantation

MRI/SPECT/Fluorescent Tri‐Modal Probe for Evaluating the Homing and Therapeutic Efficacy of Transplanted Mesenchymal Stem Cells in a Rat Ischemic Stroke Model

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