Regulating activation of transplanted cells controls tissue regeneration
- Departments of *Biologic and Materials Sciences and
- †Chemical Engineering, University of Michigan, Ann Arbor, MI 48109; and
- ‡Division of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138
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Edited by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved December 28, 2005 (received for review July 15, 2005)
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Fig. 1.Photographs of tibialis anterior muscles treated with scaffolds delivering cells and releasing HGF and FGF2 (a), scaffolds containing only HGF and FGF2 (b), and scaffolds containing only myoblasts (c). Muscles were stained to allow gross identification of regions containing donor cells (dotted lines outline positively stained tissue). Size bars are shown on the photomicrographs. (d) The mass of the muscle at 30 days after injury was greater when treated with scaffolds containing myoblasts and HGF and FGF2 (HGF/FGF2 cells in scaffold) as compared with injuries treated with an injection of myoblasts directly into the muscle [cells (injected)], blank scaffolds, scaffolds releasing growth factors without cells (HGF/FGF), or cells transplanted in scaffolds not releasing growth factors (cells in scaffold). Values represent mean and SD (n = 6). ∗, statistically significant difference (P < 0.001) compared with all other conditions.
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Fig. 2.Photomicrographs of defects 10 (a–e) and 30 days after injury (f–j). Conditions included injuries treated with an injection of myoblasts directly into the muscle (a and f), blank scaffolds (b and g), scaffolds releasing growth factors without cells (c and h), cells transplanted in scaffolds not releasing growth factors (d and i), and scaffolds delivering myoblasts and HGF and FGF2 (e and j). Defects are outlined with dotted lines. At 10 days, defects were unresolved and filled with necrotic debris in all conditions. At 30 days, the laceration injuries began to resolve in all conditions, but myoblasts delivered on scaffolds in combination with growth factors led to virtually complete resolution of the defect at this time point. Size bars are shown on the photomicrographs.
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Fig. 3.Quantitative analysis of the remaining defect area 10 (a) and 30 days after injury (b). Conditions included an injection of myoblasts directly into the muscle [cells (injected)], blank scaffolds, scaffolds releasing growth factors without cells (HGF/FGF), cells transplanted in scaffolds not releasing growth factors (cells in scaffold), and scaffolds delivering myoblasts and HGF and FGF2 (HGF/FGF2 cells in scaffold). No significant resolution of the defects occurred in any condition at 10 days. In contrast, at 30 days after injury, the defects in muscles treated with scaffolds delivering cells and growth factors were significantly smaller than in any other condition (∗, P < 0.05, as compared with all other conditions). A less-pronounced but still significant reduction in defect size was also seen in muscles treated with injected cells or scaffolds delivering HGF and FGF2 (#, P < 0.01 compared with blank scaffolds or cells transplanted on scaffolds not releasing growth factors). Values represent mean and SD (n = 6).
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Fig. 4.The width of regenerating fibers and number of centrally located nuclei at 30 days were significantly greater in muscles treated with scaffolds delivering cells and growth factors (b) as compared with scaffolds delivering only growth factors (a) or any of the other conditions. Fiber width was quantified (c), as was the number of centrally located nuclei per fiber length (d). Fiber width was increased with myoblast injection or treatment with scaffolds releasing HGF and FGF2 (#, P < 0.01 compared with blank scaffolds or scaffolds transplanting cells without growth factors) and was most dramatically increased by treatment with scaffolds delivering myoblasts and growth factors (∗, P < 0.001 compared with all other conditions). Increased centrally located nuclei per muscle length were observed only when scaffolds containing myoblasts and HGF/FGF2 were used to treat muscle injury. Values represent mean and SD (n = 6).
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Fig. 5.Photomicrographs at low (a and c) and high power (b and d) of tissue sections immunostained to identify donor myoblasts (positive staining for β-galactosidase) in the regenerating tissues. Injection of cells (c and d) leads to minimal donor cell incorporation into host musculature. In contrast, transplantation of cells on scaffolds releasing growth factors leads to extensive incorporation of donor cells into the regenerating muscle tissue (a and b). Size bars are shown on the photomicrographs.
Footnotes
- §To whom correspondence should be addressed. E-mail: mooneyd{at}deas.harvard.edu
- © 2006 by The National Academy of Sciences of the USA
