De Coppi Paolo, Callegari Andrea, Chiavegato Angela, Gasparotto Lisa, Piccoli Martina, Taiani Jenny, Pozzobon Michela, Boldrin Luisa, Okabe Masaru, Cozzi Emanuele, Atala Anthony, Gamba Piergiorgio, Sartore Saverio
Department of Pediatrics (Pediatric Oncoheamatology), University of Padua, Padua, Italy.
J Urol. 2007 Jan;177(1):369-76. doi: 10.1016/j.juro.2006.09.103.
Wound healing of the cryo-injured bladder can bring about organ remodeling because of incomplete reconstitution of depleted smooth muscle cells. Stem cell transplantation could be beneficial to improve smooth muscle cell regeneration and/or modulate the remodeling process. The repair of bladder injury using adult-type stem cells would be useful for adult urological patients but unsuited for neonatal patients, in whom major benefits are likely to derive from fetal-type stem cells.
The smooth muscle cell differentiation potential of fetal-type vs adult-type stem cells was evaluated by injecting green fluorescent protein labeled mesenchymal stem cells from rat amniotic fluid or bone marrow, respectively, in cryo-injured rat bladder walls.
At 30 days after transplantation only a few fetal-type or adult-type mesenchymal stem cells gave rise to enteric or vascular smooth muscle cells, whereas most mesenchymal stem cells appeared incapable of specific differentiation. In vitro co-culture experiments of smooth muscle cells with fetal-type or adult-type mesenchymal stem cells selectively labeled with distinct fluorochromes showed the presence of hybrid cells, suggesting that some mesenchymal stem cells can undergo cell fusion. Surprisingly the major effect of rat bone marrow or amniotic fluid mesenchymal stem cell transplantation seemed to be preventing cryo-injury induced hypertrophy of surviving smooth muscle cells.
In this model stem cell transplantation has a limited effect on smooth muscle cell regeneration. Instead it can regulate post-injury bladder remodeling, possibly via a paracrine mechanism.
由于受损的平滑肌细胞无法完全重建,冷冻损伤的膀胱伤口愈合会导致器官重塑。干细胞移植可能有助于改善平滑肌细胞再生和/或调节重塑过程。使用成人型干细胞修复膀胱损伤对成年泌尿系统疾病患者有用,但不适用于新生儿患者,对新生儿患者而言,主要益处可能来自胎儿型干细胞。
通过分别将绿色荧光蛋白标记的大鼠羊水间充质干细胞或骨髓间充质干细胞注射到冷冻损伤的大鼠膀胱壁中,评估胎儿型与成人型干细胞的平滑肌细胞分化潜能。
移植后30天,只有少数胎儿型或成人型间充质干细胞分化为肠平滑肌细胞或血管平滑肌细胞,而大多数间充质干细胞似乎无法进行特异性分化。用不同荧光染料选择性标记的胎儿型或成人型间充质干细胞与平滑肌细胞进行体外共培养实验,结果显示存在杂交细胞,这表明一些间充质干细胞可以发生细胞融合。令人惊讶的是,大鼠骨髓或羊水间充质干细胞移植的主要作用似乎是防止冷冻损伤诱导的存活平滑肌细胞肥大。
在该模型中,干细胞移植对平滑肌细胞再生的作用有限。相反,它可能通过旁分泌机制调节损伤后膀胱的重塑。