Kim Sung-Whan, Han Hoon, Chae Gue-Tae, Lee Sung-Hoon, Bo Sun, Yoon Jung-Hee, Lee Yong-Soon, Lee Kwang-Soo, Park Hwon-Kyum, Kang Kyung-Sun
Department of Pathology, College of Medicine, The Catholic University, Seoul, Korea.
Stem Cells. 2006 Jun;24(6):1620-6. doi: 10.1634/stemcells.2005-0365. Epub 2006 Feb 23.
Buerger's disease, also known as thromboangiitis obliterans, is a nonatherosclerotic, inflammatory, vasoocclusive disease. It is characterized pathologically as a panangiitis of medium and small blood vessels, including both arteries and adjacent veins, especially the distal extremities (the feet and the hands). There is no curative medication or surgery for this disease. In the present study, we transplanted human leukocyte antigen-matched human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) into four men with Buerger's disease who had already received medical treatment and surgical therapies. After the stem cell transplantation, ischemic rest pain suddenly disappeared from their affected extremities. The necrotic skin lesions were healed within 4 weeks. In the follow-up angiography, digital capillaries were increased in number and size. In addition, vascular resistance in the affected extremities, compared with the preoperative examination, was markedly decreased due to improvement of the peripheral circulation. Because an animal model of Buerger's disease is absent and also to understand human results, we transplanted human UCB-derived MSCs to athymic nude mice with hind limb ischemia by femoral artery ligation. Up to 60% of the hind limbs were salvaged in the femoral artery-ligated animals. By in situ hybridization, the human UCB-derived MSCs were detected in the arterial walls of the ischemic hind limb in the treated group. Therefore, it is suggested that human UCB-derived MSC transplantation may be a new and useful therapeutic armament for Buerger's disease and similar ischemic diseases.
血栓闭塞性脉管炎,又称伯格氏病,是一种非动脉粥样硬化性、炎症性、血管闭塞性疾病。其病理特征为中、小血管的全血管炎,包括动脉和相邻静脉,尤其是四肢远端(足部和手部)。这种疾病尚无治愈性药物或手术方法。在本研究中,我们将人类白细胞抗原匹配的人脐带血(UCB)来源的间充质干细胞(MSCs)移植到4名已接受药物治疗和手术治疗的伯格氏病男性患者体内。干细胞移植后,他们患侧肢体的缺血性静息痛突然消失。坏死的皮肤病变在4周内愈合。在随访血管造影中,指端毛细血管数量增加且管径增粗。此外,与术前检查相比,患侧肢体的血管阻力因外周循环改善而显著降低。由于缺乏伯格氏病的动物模型,同时为了了解人体研究结果,我们将人UCB来源的MSCs移植到通过股动脉结扎造成后肢缺血的无胸腺裸鼠体内。在股动脉结扎的动物中,高达60%的后肢得以挽救。通过原位杂交,在治疗组缺血后肢的动脉壁中检测到了人UCB来源的MSCs。因此,提示人UCB来源的MSC移植可能是治疗伯格氏病及类似缺血性疾病的一种新的有效治疗手段。