Tissue-engineered injectable collagen-based matrices for improved cell delivery and vascularization of ischemic tissue using CD133+ progenitors expanded from the peripheral blood.
BACKGROUND
The use of stem and/or progenitor cells to achieve potent vasculogenesis in humans has been hindered by low cell numbers, implant capacity, and survival. This study investigated the expansion of CD133+ cells and the use of an injectable collagen-based tissue engineered matrix to support cell delivery and implantation within target ischemic tissue.


RESULTS
Adult human CD133+ progenitor cells from the peripheral blood were generated and expanded by successive removal and culture of CD133- cell fractions, and delivered within an injectable collagen-based matrix into the ischemic hindlimb of athymic rats. Controls received injections of phosphate-buffered saline, matrix, or CD133+ cells alone. Immunohistochemistry of hindlimb muscle 2 weeks after treatment revealed that the number of CD133+ cells retained within the target site was >2-fold greater when delivered by matrix than when delivered alone (P<0.01). The transplanted CD133+ cells incorporated into vascular structures, and the matrix itself also was vascularized. Rats that received matrix and CD133+ cells demonstrated greater intramuscular arteriole and capillary density than other treatment groups (P<0.05 and P<0.01, respectively).


CONCLUSIONS
Compared with other experimental approaches, treatment of ischemic muscle tissue with generated CD133+ progenitor cells delivered in an injectable collagen-based matrix significantly improved the restoration of a vascular network. This work demonstrates a novel approach for the expansion and delivery of blood CD133+ cells with resultant improvement of their implantation and vasculogenic capacity.
Suuronen
Erik J
EJ
Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin St, Laboratory H553, Ottawa, Ontario, Canada, K1Y 4W7.
Veinot
John P
JP
Wong
Serena
S
Kapila
Varun
V
Price
Joel
J
Griffith
May
M
Mesana
Thierry G
TG
Ruel
Marc
M
D000071916:AC133 Antigen; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D001160:Arterioles; D002196:Capillaries; D002448:Cell Adhesion; D002469:Cell Separation; D002478:Cells, Cultured / Q000166:cytology / Q000637:transplantation; D003094:Collagen; D005109:Extracellular Matrix / Q000737:chemistry / Q000637:transplantation*; D006023:Glycoproteins / Q000032:analysis*; D006614:Hindlimb / Q000098:blood supply*; D006801:Humans; D016130:Immunophenotyping; D007273:Injections, Intramuscular; D007511:Ischemia / Q000601:surgery*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology*; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000032:analysis*; D036102:Peripheral Blood Stem Cell Transplantation; D051381:Rats; D011923:Rats, Nude; D023822:Tissue Engineering; D014183:Transplantation, Heterologous
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606025:Prom1 protein, rat; D003094:Collagen