Strategy for clinical setting in intramuscular and subcutaneous islet transplantation

Sakata, Naoaki; Aoki, Takeshi; Yoshimatsu, Gumpei; Tsuchiya, Hideo; Hata, Tatsuo; Katayose, Yu; Egawa, Shinichi; Unno, Michiaki

doi:10.1002/dmrr.2463

Cited by 92 publications

(97 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The advantages of subcutaneous implantation are as follows: minimally invasive surgery and the possibility to easily monitor islets. However, the subcutaneous vascular network is inadequate and needs to be enhanced for successful engraftment [8–10]. Pancreatic islets are sensitive to hypoxia, which is even emphasised in environments with high concentrations of glucose typical of a diabetic recipient.…”

Section: Introductionmentioning

confidence: 99%

Multimodal Imaging Reveals Improvement of Blood Supply to an Artificial Cell Transplant Site Induced by Bioluminescent Mesenchymal Stem Cells

et al. 2016

View full text Add to dashboard Cite

PurposeAn artificial site for cell or pancreatic islet transplantation can be created using a polymeric scaffold, even though it suffers subcutaneously from improper vascularisation. A sufficient blood supply is crucial for graft survival and function and can be enhanced by transplantation of mesenchymal stem cells (MSCs). The purpose of this study was to assess the effect of syngeneic MSCs on neoangiogenesis and cell engraftment in an artificial site by multimodal imaging.ProceduresMSCs expressing a gene for luciferase were injected into the artificial subcutaneous site 7 days after scaffold implantation. MRI experiments (anatomical and dynamic contrast-enhanced images) were performed on a 4.7-T scanner using gradient echo sequences. Bioluminescent images were acquired on an IVIS Lumina optical imager. Longitudinal examination was performed for 2 months, and one animal was monitored for 16 months.ResultsWe confirmed the long-term presence (lasting more than 16 months) of viable donor cells inside the scaffolds using bioluminescence imaging with an optical signal peak appearing on day 3 after MSC implantation. When compared to controls, the tissue perfusion and vessel permeability in the scaffolds were significantly improved at the site with MSCs with a maximal peak on day 9 after MSC transplantation.ConclusionsOur data suggest that the maximal signal obtained by bioluminescence and magnetic resonance imaging from an artificially created site between 3 and 9 days after MSC transplantation can predict the optimal time range for subsequent cellular or tissue transplantation, including pancreatic islets.

show abstract

Section: Introductionmentioning

confidence: 99%

Multimodal Imaging Reveals Improvement of Blood Supply to an Artificial Cell Transplant Site Induced by Bioluminescent Mesenchymal Stem Cells

et al. 2016

View full text Add to dashboard Cite

show abstract

“…8,12,[14][15][16] It has been suggested that the lack of graft viability post-subcutaneous transplantation is due to the tissue's relatively low superficial tissue oxygen tension compared to other vascularized organs. 16 To thwart endogenous hypoxia and improve islet engraftment, subcutaneous engraftment strategies have employed growth factors, 17 scaffolds, 18-20 encapsulation polymers, 15,21 immunoisolating and non-immunoisolating devices, 11,[22][23][24][25][26] and oxygen delivery technologies. 17,24 While attractive due to the potential of avoiding systemic immunosuppression, a drawback of immunoisolating devices is the physical separation between host nutrient supply and the therapeutic cells within the device.…”

Section: Discussionmentioning

confidence: 99%

Long-term function and optimization of mouse and human islet transplantation in the subcutaneous device-less site

Pepper

Bruni

Pawlick

et al. 2016

Islets

View full text Add to dashboard Cite

Clinical islet transplantation has routinely been demonstrated to be an efficacious means of restoring glycemic control in select patients with autoimmune diabetes. Notwithstanding marked progress and improvements, the broad-spectrum application of this treatment option is restricted by the complications associated with intrahepatic portal cellular infusion and the scarcity of human donor pancreata. Recent progress in stem cell biology has demonstrated that the potential to expand new b cells for clinical transplantation is now a reality. As such, research focus is being directed toward optimizing safe extrahepatic transplant sites to house future alternative b cell sources for clinical use. The present study expands on our previous development of a prevascularized subcutaneous device-less (DL) technique for cellular transplantation, by demonstrating long-term (>365 d) durable syngeneic murine islet graft function. Furthermore, histological analysis of tissue specimens collected immediately post-DL site creation and acutely post-human islet transplantation demonstrates that this technique results in close apposition of the neovascularized collagen to the transplanted cells without dead space, thereby avoiding hypoxic luminal dead-space. Murine islets transplanted into the DL site created by a larger luminal diameter (6-Fr.) (n D 11), reversed diabetes to the similar capacity as our standard DL method (5-Fr.)(n D 9). Furthermore, glucose tolerance testing did not differ between these 2 transplant groups (p > 0 .05). Taken together, this further refinement of the DL transplant approach facilitates a simplistic means of islet infusion, increases the transplant volume capacity and may provide an effective microenvironment to house future alternative b cell sources.

show abstract

“…However, hypoxic conditions in intramuscular and subcutaneous spaces have been reported to reduce the survival of transplanted islet cells [94–96]. To overcome this problem, artificially modified islet cells transplanted into intramuscular and subcutaneous spaces have been studied.…”

Section: Islet Cell Transplantationmentioning

confidence: 99%

Transgene and islet cell delivery systems using nano-sized carriers for the treatment of diabetes mellitus

Ookawara

Ishibashi

et al. 2017

Nano Reviews & Experiments

View full text Add to dashboard Cite

Gene therapy that targets the pancreas and intestines with delivery systems using nano-sized carriers such as viral and non-viral vectors could improve the control of blood glucose levels, resulting in an improved prognosis for patients with diabetes mellitus. Allogenic pancreatic islet cell transplantations using such delivery systems have been developed as therapeutic options for diabetes mellitus. This review focuses on transgenes and islet cell delivery systems using nano-sized carriers for the treatment of diabetes mellitus.

show abstract

Strategy for clinical setting in intramuscular and subcutaneous islet transplantation

Cited by 92 publications

References 95 publications

Multimodal Imaging Reveals Improvement of Blood Supply to an Artificial Cell Transplant Site Induced by Bioluminescent Mesenchymal Stem Cells

Multimodal Imaging Reveals Improvement of Blood Supply to an Artificial Cell Transplant Site Induced by Bioluminescent Mesenchymal Stem Cells

Long-term function and optimization of mouse and human islet transplantation in the subcutaneous device-less site

Transgene and islet cell delivery systems using nano-sized carriers for the treatment of diabetes mellitus

Contact Info

Product

Resources

About