Biodegradable polymer composite grafts promote the survival and differentiation of retinal progenitor cells.
Retinal progenitor cells (RPCs) are multipotent central nervous system precursors that give rise to all of the cell types of the retina during development. Several groups have reported that mammalian RPCs can be isolated and expanded in culture and can differentiate into retinal neurons upon grafting to the mature, diseased eye. However, cell delivery and survival remain formidable obstacles to application of RPCs in a clinical setting. Because biodegradable polymer/progenitor constructs have been shown to be capable of tissue generation in other compartments, we evaluated the survival, migration, and differentiation of RPCs delivered on PLLA/PLGA polymer substrates to the mouse subretinal space and compared these results to conventional injections of RPCs. Polymer composite grafts resulted in a near 10-fold increase in the number of surviving cells after 4 weeks, with a 16-fold increase in cell delivery. Grafted RPCs migrated into the host retina and expressed the mature markers neurofilament-200, glial fibrillary acidic protein, protein kinase C-alpha, recoverin, and rhodopsin. We conclude that biodegradable polymer/progenitor cell composite grafts provide an effective means of increasing progenitor cell survival and overall yield when transplanting to sites within the central nervous system such as the retina.
Tomita
Minoru
M
The Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02111, USA.
Lavik
Erin
E
Klassen
Henry
H
Zahir
Tasneem
T
Langer
Robert
R
Young
Michael J
MJ
D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D004195:Disease Models, Animal; D006085:Graft Survival; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D012160:Retina / Q000166:cytology* / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D001672:Biocompatible Materials; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)