Locally enhanced angiogenesis promotes transplanted cell survival.
A developing therapy for complete or partial loss of function in various tissues and organs involves transplanting an appropriate cell population, capable of compensating for the existing deficiencies. Clinical application of this type of strategy is currently limited by the death or dedifferentiation of the transplanted cells after delivery to the recipient. A delay in thorough vascularization of the implant area creates an environment low in oxygen and other nutrients, and likely contributes to the initial death of transplanted cells. We have addressed this problem by sustained delivery of vascular endothelial growth factor (VEGF), an initiator of angiogenesis, from a porous polymer matrix utilized simultaneously for cell delivery. As expected from previous studies, VEGF delivered from these constructs elicited an enhanced angiogenic response over a 2-week period when implanted subcutaneously in SCID mice. Hepatocytes implanted using VEGF-containing matrices demonstrated significantly greater survival after 1 week in vivo as compared with cells implanted on matrices without growth factor. The results of this study therefore indicate that enhancing vascularization in the location of transplanted cells promotes their survival. In addition, this delivery system may be used in future studies to directly promote cell survival and function by also providing growth factors specific to the transplanted cells.
Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Molly K
MK
Smith
Martin C
MC
Peters
Thomas P
TP
Richardson
Jessica C
JC
Garbern
David J
DJ
Mooney
D043925:Angiogenesis Inducing Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D022781:Hepatocytes / Q000637:transplantation*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000493:pharmacokinetics / Q000494:pharmacology*
D043925:Angiogenesis Inducing Agents; D042461:Vascular Endothelial Growth Factor A