美國研究團隊已發現利用病人自己的骨髓間葉幹細胞(MSC)來再生膀胱的醫學模式。這項發佈在《幹細胞》期刊上的研究特別與有非正常發育膀胱的幼兒有關，而且它代表向新器官移植療法邁出了新一步。
這項研究由西北大學範伯格醫學學校和兒童紀念研究中心Arun Sharma博士和Earl Cheng博士引導，以前對細胞再生能力的研究主要是在動物模型上，這些不能很好的被臨床所使用。
“對病人身上骨髓幹細胞的合理使用，為探索器官移植療法，尤其是膀胱再生，打開了新的道路。”高級專家Sharma說，“我們研究中的一些發現證明了這些采自骨髓的幹細胞的可塑性，這使他們成為這類工作的理想之選。”
研究小組發現骨髓間葉幹細胞（MSCs）在表面和生理上和膀胱光滑肌肉細胞（bSMCs）相似，這意味著MSCs可以作為有遭破壞風險的bSMCs的細胞替換。
“為了研究，我們開發了一種以靈長類動物為基礎的模型，把狒狒的膀胱和骨髓MSCs聯繫在一起去嘗試局部的膀胱再生，”Sharma說，“我們發現被整個研究使用的間葉幹細胞保持著在移植部位的穩定性，手術後10個星期依然保持活力。”
移植的骨髓細胞也保持著發揮光滑肌細胞主要特性的能力，有一個類似正常膀胱一樣的不間斷的收縮週期。
當前有關支配膀胱再生的細胞和分子之間的作用的資訊是很罕見的，然而該小組的研究演示了MSCs在局部膀胱再生的可行性，而且他們所使用的靈長性動物的模型給這些過程提供了有價值的見解。它們也可能被用到人身上。
“這個新發現的膀胱增殖模式給膀胱再生過程展現一個獨特的見解，而且強有力地證明了MSCs可以被組織工程學目的使用。”Sharma總結道，“這項研究中的非人類靈長動物膀胱增殖模型的建立也將進一步提供重要的非臨床數據，這些可能最終會被臨床所利用。”
“在生物工程上，膀胱修復不是一個簡單的事情。臨床的SIS材料和病人提供的MSCs的組合給進一步測試提供了一個很好組合”，《幹細胞》副總編Mark Pittenger說，“Sharma博士和他的同事推進了Anthony Atala博士的工作。在過去的幾年裏這個領域的進展是十分顯而易見的，並且更多臨床研究還是需要的。”
Scientists Use Bone Marrow MSCs for Partial Bladder Regeneration in Primates
Researchers in the U.S. reported on the development of a new technique that uses bone marrow mesenchymal stem cells (MSCs) to partially regenerate bladder tissue in nonhuman primates. They hope their achievement will provide new insights into the bladder-regeneration process in vivo, and ultimately lead to new approaches to correcting developmental bladder abnormalities in pediatric patients. The studies, reported by Arun Sharma, Ph.D., and Earl Cheng, Ph.D., from the Feinberg School of Medicine at Northwestern University, are published in Stem Cells, in a paper titled, A Non-Human Primate Model for Urinary Bladder Regeneration Utilizing Autologous Sources of Bone Marrow Derived Mesenchymal Stem Cells.
Therapeutic approaches to address developmental urinary bladder abnormalities in pediatric patients have to date relied heavily on surgical intervention in the form of bladder-augmentation cystoplasty, Drs. Sharma, Cheng, and colleagues report. However, the technique is beset by drawbacks and can only be considered a stopgap measure. Moreover, they add, clinical attempts to create functional bladder tissue and overcome the problems associated with traditional bladder augmentation have also been met by numerous obstacles. One such technique has used myelomeningocele patient-derived urothelial and bladder smooth muscle cells (bSMCs) to reconstruct the urothelium and smooth muscle components of the bladder. Although highly innovative in approach, the authors admit, “these studies demonstrated lackluster physiological effects and did not address the possibility that the use of pathologic bladder cells may eventually result in the reformation of a diseased bladder state as well as the decline in urodynamic function of patients undergoing this treatment.”
Drs. Sharma and Cheng’s approach instead used bone marrow MSCs that in a clinical setting would be taken from the patient. They found that such cells have both phenotypic and physiological similarities with bSMCs, which they hypothesized could allow the cells to serve as an alternative source of cells for damaged bSMCs.
“For our research we developed a primate-based model, using a baboon bladder in conjunction with bone marrow MSCs to attempt partial bladder regeneration,” Sharma explains. “We found that the mesenchymal stem cells used throughout the study retained the ability to populate a surgically grafted area while remaining active 10 weeks after surgery.”
The researchers hope their approach could provide valuable new insight into the cellular and molecular interactions that govern bladder regeneration. “The newly described bladder-augmentation model represents a unique insight into the bladder-regeneration process and provides strong evidence that MSCs can be exploited for tissue-engineering purposes,” Sharma concludes. “The nonhuman primate bladder-augmentation model established in this study will also further provide key preclinical data that may eventually be translated in a clinical setting.”
