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Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold

View Article: PubMed Central - PubMed

ABSTRACT

Transplantation of pancreatic islets is a therapeutic option to preserve or restore β-cell function. Our study was aimed at developing a clinically applicable protocol for extrahepatic transplantation of pancreatic islets. The potency of islets implanted onto the omentum, using an in situ–generated adherent, resorbable plasma-thrombin biologic scaffold, was evaluated in diabetic rat and nonhuman primate (NHP) models. Intraomental islet engraftment in the biologic scaffold was confirmed by achievement of improved metabolic function and preservation of islet cytoarchitecture, with reconstitution of rich intrainsular vascular networks in both species. Long-term nonfasting normoglycemia and adequate glucose clearance (tolerance tests) were achieved in both intrahepatic and intraomental sites in rats. Intraomental graft recipients displayed lower levels of serum biomarkers of islet distress (e.g., acute serum insulin) and inflammation (e.g., leptin and α2-macroglobulin). Importantly, low-purity (30:70% endocrine:exocrine) syngeneic rat islet preparations displayed function equivalent to that of pure (>95% endocrine) preparations after intraomental biologic scaffold implantation. Moreover, the biologic scaffold sustained allogeneic islet engraftment in immunosuppressed recipients. Collectively, our feasibility/efficacy data, along with the simplicity of the procedure and the safety of the biologic scaffold components, represented sufficient preclinical testing to proceed to a pilot phase I/II clinical trial.

No MeSH data available.


Intraomental islet implantation within a biologic scaffold. A: Schematic diagram of the transplant procedure. B: Procedure in rat. C: Procedure in NHP. After midline laparotomy (b1), the omentum is gently exteriorized and opened (b2 and c1). The islet graft, resuspended in autologous plasma (c2), is gently distributed onto the omentum (b3 and c3). Recombinant human thrombin is added onto the islets on the omental surface to induce gel formation (c4), and then the omentum is folded to increase the contact of the graft to the vascularized omentum (b4 and c5). Nonresorbable stitches were placed on the far outer margins of the graft in the NHP (c5) for easier identification of the graft area at the time of graft removal.
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Figure 1: Intraomental islet implantation within a biologic scaffold. A: Schematic diagram of the transplant procedure. B: Procedure in rat. C: Procedure in NHP. After midline laparotomy (b1), the omentum is gently exteriorized and opened (b2 and c1). The islet graft, resuspended in autologous plasma (c2), is gently distributed onto the omentum (b3 and c3). Recombinant human thrombin is added onto the islets on the omental surface to induce gel formation (c4), and then the omentum is folded to increase the contact of the graft to the vascularized omentum (b4 and c5). Nonresorbable stitches were placed on the far outer margins of the graft in the NHP (c5) for easier identification of the graft area at the time of graft removal.

Mentions: Under general anesthesia, a substernal midline minilaparotomy allowed exteriorizing the omentum that was spread flat over a sterile field (Fig. 1). We previously reported a similar intraomental flap transplant procedure in NHP (22).


Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold
Intraomental islet implantation within a biologic scaffold. A: Schematic diagram of the transplant procedure. B: Procedure in rat. C: Procedure in NHP. After midline laparotomy (b1), the omentum is gently exteriorized and opened (b2 and c1). The islet graft, resuspended in autologous plasma (c2), is gently distributed onto the omentum (b3 and c3). Recombinant human thrombin is added onto the islets on the omental surface to induce gel formation (c4), and then the omentum is folded to increase the contact of the graft to the vascularized omentum (b4 and c5). Nonresorbable stitches were placed on the far outer margins of the graft in the NHP (c5) for easier identification of the graft area at the time of graft removal.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC5384628&req=5

Figure 1: Intraomental islet implantation within a biologic scaffold. A: Schematic diagram of the transplant procedure. B: Procedure in rat. C: Procedure in NHP. After midline laparotomy (b1), the omentum is gently exteriorized and opened (b2 and c1). The islet graft, resuspended in autologous plasma (c2), is gently distributed onto the omentum (b3 and c3). Recombinant human thrombin is added onto the islets on the omental surface to induce gel formation (c4), and then the omentum is folded to increase the contact of the graft to the vascularized omentum (b4 and c5). Nonresorbable stitches were placed on the far outer margins of the graft in the NHP (c5) for easier identification of the graft area at the time of graft removal.
Mentions: Under general anesthesia, a substernal midline minilaparotomy allowed exteriorizing the omentum that was spread flat over a sterile field (Fig. 1). We previously reported a similar intraomental flap transplant procedure in NHP (22).

View Article: PubMed Central - PubMed

ABSTRACT

Transplantation of pancreatic islets is a therapeutic option to preserve or restore β-cell function. Our study was aimed at developing a clinically applicable protocol for extrahepatic transplantation of pancreatic islets. The potency of islets implanted onto the omentum, using an in situ–generated adherent, resorbable plasma-thrombin biologic scaffold, was evaluated in diabetic rat and nonhuman primate (NHP) models. Intraomental islet engraftment in the biologic scaffold was confirmed by achievement of improved metabolic function and preservation of islet cytoarchitecture, with reconstitution of rich intrainsular vascular networks in both species. Long-term nonfasting normoglycemia and adequate glucose clearance (tolerance tests) were achieved in both intrahepatic and intraomental sites in rats. Intraomental graft recipients displayed lower levels of serum biomarkers of islet distress (e.g., acute serum insulin) and inflammation (e.g., leptin and α2-macroglobulin). Importantly, low-purity (30:70% endocrine:exocrine) syngeneic rat islet preparations displayed function equivalent to that of pure (>95% endocrine) preparations after intraomental biologic scaffold implantation. Moreover, the biologic scaffold sustained allogeneic islet engraftment in immunosuppressed recipients. Collectively, our feasibility/efficacy data, along with the simplicity of the procedure and the safety of the biologic scaffold components, represented sufficient preclinical testing to proceed to a pilot phase I/II clinical trial.

No MeSH data available.