Therapeutic angiogenesis by a myoblast layer harvested by tissue transfer printing from cell-adhesive, thermosensitive hydrogels.
Peripheral arterial disease (PAD) is characterized by the altered structure and function of arteries caused by accumulated plaque. There have been many studies on treating this disease by the direct injection of various types of therapeutic cells, however, the low cell engraftment efficiency and diffusion of the transplanted cells have been major problems. In this study, we developed an approach (transfer printing) to deliver monolayer of cells to the hindlimb ischemic tissue using thermosensitive hydrogels, and investigated its efficacy in long term retention upon transplantation and therapeutic angiogenesis. We first investigated the in vitro maintenance of robust cell-cell contacts and stable expression of the ECM proteins in myoblast layer following transfer printing process. In order to confirm the therapeutic effect of the myoblasts in vivo, we cultured a monolayer of C2C12 myoblasts on thermosensitive hydrogels, which was then transferred to the hindlimb ischemia tissue of athymic mice directly from the hydrogel by conformal contact. The transferred myoblast layer was retained for a longer period of time than an intramuscularly injected cell suspension. In addition, the morphology of the mice and laser Doppler perfusion (28 days after treatment) supported that the myoblast layer enhanced the therapeutic effects on the ischemic tissue. In summary, the transplantation of the C2C12 myoblast layer using a tissue transfer printing method could represent a new approach for the treatment of PAD by therapeutic angiogenesis.
Department of Bioengineering, College of Engineering, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea.
Dong Wan
DW
Kim
Indong
I
Jun
Tae-Jin
TJ
Lee
Ji Hye
JH
Lee
Young Jun
YJ
Lee
Hyeon-Ki
HK
Jang
Seokyung
S
Kang
Ki Dong
KD
Park
Seung-Woo
SW
Cho
Byung-Soo
BS
Kim
Heungsoo
H
Shin
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D005260:Female; D006614:Hindlimb / Q000473:pathology; D020100:Hydrogels / Q000737:chemistry*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D032446:Myoblasts / Q000166:cytology* / Q000637:transplantation
D020100:Hydrogels
Ischemia; Myoblasts; Therapeutic angiogenesis; Thermosensitive hydrogels; Transfer printing