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干细胞疗法:系统性硬化症治疗的未来?一例病例报告。

Stem cells therapy: the future in the management of systemic sclerosis? A case report.

作者信息

Song Jung In, Volz Silvanie, Liodaki Maria Eirini, Mailänder Peter, Kalousis Konstantinos

机构信息

Clinic of Plastic, Hand Surgery and Burn Care Unit, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.

出版信息

Hell J Nucl Med. 2017 Sep-Dec;20 Suppl:164.

Abstract

OBJECTIVE

Systemic sclerosis (SSc) is a connective tissue disorder of unknown etiology, with heterogeneous clinical manifestations and chronic and often progressive course. The diffuse cutaneous form of SSc (dcSSc) is characterized by thickening of the skin (scleroderma) and distinctive involvement of multiple internal organs. Patients with limited cutaneous SSc (lcSSc) generally have long-standing Raynaud's phenomenon before other manifestations of SSc appear. Over the last decade the Interest of adipose-derived cell therapy in regenerative medicine has increased continuously. In compare to bone marrow-derived mesenchymal stem cells (MSCs) adipose tissue-derived stem cells (ADSCs) are considered to be ideal for application in regenerative medicine. Zuk et al., introduced a multipotent, undifferentiated, self-renewing progenitor cell population isolated from adipose tissue, called processed lipoaspirate (PLA). However, subcutaneous injections of autologous adipose tissue-derived stromal vascular fraction (ADSVF), which is known to contain mesenchymal stem cells, in hands of Patients with scleroderma for enhancing their impaired hand function is still in an experimental stage, although there are already promising results of the therapy. Commonly available therapeutic options for hands of Patients with systemic sclerosis, vasodilatator drugs and physiotherapy, have many restriction and limited effects.

MATERIALS AND METHOD

A 62 years old woman with scleroderma presented with progressive digital necrosis, ulceration, gangrene and impaired wound healing, despite of conventional therapy with vasodilatator drugs. Water-jet-Assisted Liposuction (Body-jet® evo, human med AG, Schwerin, Germany) of subcutaneous abdominal fat was carried out under general anesthesia by an experienced surgeon. Autologous adipose tissue-derived stromal vascular fraction (ADSVF) was harvested by in a single-use Q-graft® collector (human med AG, Schwerin, Germany). Cells were centrifuged in 400G for 5 minutes and cell pellets were aspirated carefully in a 20mL syringe filled with 0.9% NaCl. A total of ca. 2.72 million cells have been isolated. Meanwhile middle phalangeal amputation of digit 2, 3 and 4 of the left hand were performed, without closing the skin of the amputation stumps. The SVF cell suspension was injected subcutaneous into the area of metacarpophalangeal joints in both hands, as well as into the amputation stump of the left middle finger, and under a skin necrosis in the right hand.

RESULTS

The therapy was good tolerated by the patient, with absence of adverse reactions. No infection was observed, despite open amputation. Three weeks after the stem cell therapy, no need to further amputation was demonstrated. The patient is still under regular clinical observation, in order to determine the long term effects of the therapy.

CONCLUSION

Application of isolated adipose tissue-derived stem cells seems to be a very promising procedure in the treatment of the manifestation of systemic sclerosis. However, more clinical and experimental studies are required, in order to understand the exact mechanisms of action and standardize the therapy.

摘要

目的

系统性硬化症(SSc)是一种病因不明的结缔组织疾病,临床表现多样,病程慢性且常呈进行性。弥漫性皮肤型SSc(dcSSc)的特征是皮肤增厚(硬皮病)以及多个内脏器官有明显受累。局限性皮肤型SSc(lcSSc)患者通常在SSc的其他表现出现之前就有长期的雷诺现象。在过去十年中,脂肪源性细胞疗法在再生医学中的应用兴趣持续增加。与骨髓间充质干细胞(MSCs)相比,脂肪组织源性干细胞(ADSCs)被认为是再生医学应用的理想选择。Zuk等人从脂肪组织中分离出一种多能、未分化、自我更新的祖细胞群,称为处理过的脂肪抽吸物(PLA)。然而,皮下注射已知含有间充质干细胞的自体脂肪组织源性基质血管成分(ADSVF)以改善硬皮病患者受损的手部功能仍处于实验阶段,尽管该疗法已经有了令人鼓舞的结果。系统性硬化症患者手部常用的治疗方法,如血管扩张药物和物理治疗,有许多限制且效果有限。

材料与方法

一名62岁的硬皮病女性患者,尽管接受了血管扩张药物的常规治疗,但仍出现进行性手指坏死、溃疡、坏疽及伤口愈合受损。由经验丰富的外科医生在全身麻醉下对腹部皮下脂肪进行水刀辅助吸脂(Body-jet® evo,human med AG,德国什未林)。通过一次性Q-graft®收集器(human med AG,德国什未林)收获自体脂肪组织源性基质血管成分(ADSVF)。细胞以400G离心5分钟,小心地将细胞沉淀抽吸到装有0.9%氯化钠的20mL注射器中。共分离出约272万个细胞。同时,对左手的第2、3和4指进行了中节指骨截肢,截肢残端皮肤未缝合。将SVF细胞悬液皮下注射到双手的掌指关节区域以及左手食指的截肢残端和右手皮肤坏死下方。

结果

患者对该治疗耐受性良好,未出现不良反应。尽管是开放性截肢,但未观察到感染。干细胞治疗三周后,无需进一步截肢。患者仍在接受定期临床观察,以确定该治疗的长期效果。

结论

应用分离的脂肪组织源性干细胞在治疗系统性硬化症的表现方面似乎是一种非常有前景的方法。然而,需要更多的临床和实验研究,以了解确切的作用机制并规范该治疗方法。

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