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Restorative Medicine
Cell Encapsulation May Hold the Key to Preventing Cell Transplant Rejection
Cell Encapsulation May Hold the Key to Preventing Cell Transplant Rejection
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Cell transplantation is a promising option for the management of endocrine disorders such as type I diabetes and testosterone deficiency, but risk of rejection by the recipient’s immune system and the resulting life-long dependency on immunosuppressive drugs has been a major obstacle to long-term success.
In order to protect transplanted cells and improve cell viability, several research groups have tried encapsulating the cells within a capsule that acts as a physical barrier. However, issues with inadequate blood supply and oxygen permeability within the capsule have limited their ability to support the transplanted cells.
Alessandro Grattoni, PhD
A. Osama Gaber, MD
A Houston Methodist research team of nanomedicine and cell transplant experts led by Alessandro Grattoni, PhD, Frank J. and Jean Raymond Centennial Chair in the department of nanomedicine, has developed a novel encapsulation platform for transplanted cells termed neovascularized implantable cell homing and encapsulation or NICHE that directly addresses these limitations.
“Unlike other encapsulation platforms, NICHE successfully integrates blood supply, oxygenation and localized immunosuppressant drug delivery into one device. This has significantly improved cell viability, while avoiding the adverse effects of systemic immunosupression.”
Alessandro Grattoni, PhD
Chair, Department of Nanomedicine Houston Methodist
NICHE is implanted just under the skin, permitting easy access for replenishing transplanted cells or drugs when needed. The researchers utilized 3-D printing technology to create the NICHE platform as it allows easy customization based on cell type and rapid, cost-effective scalability.
In a preclinical study published in Biomaterials, Grattoni and his team successfully used NICHE to transplant testosterone-producing testicular Leydig cells, offering a potential new treatment option for testosterone deficiency. The NICHE platform effectively established blood supply within the capsule and achieved sustained immunosuppressant delivery. Promisingly, the transplanted cells remained viable for the length of the study. Building upon their work with Leydig cells, the team is evaluating the efficacy of pancreatic islet cell transplantation using NICHE in preclinical diabetes models.
“These findings are a culmination of a long history of collaboration in cellular transplantation research at Houston Methodist and should expedite the translation of cell encapsulation technology from the lab to the clinic, delivering more effective treatment options to patients with conditions like type I diabetes.”
A. Osama Gaber, MD
John F. Jr. and Carolyn Bookout Presidential Distinguished Chair in Surgery, Department of Surgery Houston Methodist
Credit: Biomaterials Fig. 1. NICHE deployment strategy. (A) Mesenchymal Stem Cells (MSCs) hydrogel-filled NICHE is implanted in a subcutaneous pocket to stimulate vascularization. (B) Pre-vascularization phase, with blood vessel formation across the cell reservoir. (C) Transcutaneous loading of immunosuppressant into NICHE drug reservoir using loading and venting needles. Needles are advanced into the NICHE drug reservoir through self-sealing silicon ports (visible in Fig. 2). Upon drug loading, the venting needle permits flushing of the reservoir and removal of entrapped air or liquid. (D) Transcutaneous transplantation of cells into the vascularized and immunosuppressed cell reservoir using a needle connected to a cell-loaded syringe.
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