Induction of smooth muscle cell-like phenotype in marrow-derived cells among regenerating urinary bladder smooth muscle cells.
Tissue regeneration on acellular matrix grafts has great potential for therapeutic organ reconstruction. However, hollow organs such as the bladder require smooth muscle cell regeneration, the mechanisms of which are not well defined. We investigated the mechanisms by which bone marrow cells participate in smooth muscle formation during urinary bladder regeneration, using in vivo and in vitro model systems. In vivo bone marrow cells expressing green fluorescent protein were transplanted into lethally irradiated rats. Eight weeks following transplantation, bladder domes of the rats were replaced with bladder acellular matrix grafts. Two weeks after operation transplanted marrow cells repopulated the graft, as evidenced by detection of fluorescent staining. By 12 weeks they reconstituted the smooth muscle layer, with native smooth muscle cells (SMC) infiltrating the graft. In vitro, the differential effects of distinct growth factor environments created by either bladder urothelial cells or bladder SMC on phenotypic changes of marrow cells were examined. First, supernatants of cultured bladder cells were used as conditioned media for marrow cells. Second, these conditions were reconstituted with exogenous growth factors. In each case, a growth factor milieu characteristic of SMC induced an SMC-like phenotype in marrow cells, whereas that of urothelial cells failed. These findings suggest that marrow cells differentiate into smooth muscle on acellular matrix grafts in response to the environment created by SMC.
Kanematsu
Akihiro
A
Department of Urology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaracho, Sakyo, Kyoto, Japan 606-8507.
Yamamoto
Shingo
S
Iwai-Kanai
Eri
E
Kanatani
Isao
I
Imamura
Masaaki
M
Adam
Rosalyn M
RM
Tabata
Yasuhiko
Y
Ogawa
Osamu
O
D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D049109:Cell Proliferation; D017077:Culture Media, Conditioned / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D008856:Microscopy, Fluorescence; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013997:Time Factors; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing
D017077:Culture Media, Conditioned; D006133:Growth Substances; D049452:Green Fluorescent Proteins