Advances in stem cell transplantation for thromboangiitis obliterans_West China Medical Journal

Authors：

YANG Jinjiang ^1,2 ,  YANG Yong ^1,2 , MA Zhenhuan ^1,2

1. Department of Vascular Surgery, the Fourth Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650000, P. R. China;
2. Vascular Surgery Center of Yunnan Province, Kunming, Yunnan 650000, P. R. China;

Corresponding?author：

YANG Yong, Email: yncvs126@126.com

Keywords：

Stem cell transplant; Thromboangiitis obliterans; Clinical research; Efficacy evaluation; Serious adverse event

DOI：

10.7507/1002-0179.201912123

Video：

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Abstract Full text Figures/Tables Video References Cited by

Stem cell transplantation is one of the main methods to treat thromboangiitis obliterans (TAO). In recent years, research on the treatment mechanism of stem cell transplantation has made some progress. The results of a number of stem cell clinical trials specifically for TAO have been published. Some new stem cell types have gradually been used in the clinic. There is no major dispute over security. In addition, research shows that the efficacy of stem cell transplantation is affected in many ways, and some factors have a certain predictive effect on the possibility of amputation after transplantation. This paper reviews the clinical research progress of stem cell transplantation for TAO, and aims to provide some basis for the better use of stem cell transplantation in the treatment of TAO.

Citation： YANG Jinjiang, YANG Yong, MA Zhenhuan. Advances in stem cell transplantation for thromboangiitis obliterans. West China Medical Journal, 2020, 35(3): 357-362. doi: 10.7507/1002-0179.201912123 Copy

1.	Folkman J. Therapeutic angiogenesis in ischemic limbs. Circulation, 1998, 97(12): 1108-1110.
2.	Tateishi-Yuyama E, Matsubara H, Murohara T, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study anda randomised controlled trial. Lancet, 2002, 360(9331): 427-435.
3.	中華醫學會醫學工程學分會干細胞工程專業委員會, 中華醫學會外科學分會血管外科學組. 自體干細胞移植規范化治療下肢慢性缺血性疾病的專家共識. 中華細胞與干細胞雜志 (電子版), 2012, 2(1): 1-4.
4.	Dong Z, Pan T, Fang Y, et al. Purified CD34⁺ cells versus peripheral blood mononuclear cells in the treatment of angiitis-induced no-option critical limb ischaemia: 12-month results of a prospective randomised single-blinded non-inferiority trial. EBioMedicine, 2018, 35: 46-57.
5.	Fang Y, Wei Z, Chen B, et al. A five-year study of the efficacy of purified CD34⁺ cell therapy for angiitis-induced no-option critical limb ischemia. Stem Cells Transl Med, 2018, 7(8): 583-590.
6.	Martin-Rufino JD, Lozano FS, Redondo AM, et al. Sequential intravenous allogeneic mesenchymal stromal cells as a potential treatment for thromboangiitis obliterans (Buerger’s disease). Stem Cell Res Ther, 2018, 9(1): 150.
7.	Ra JC, Jeong EC, Kang SK, et al. A prospective, nonrandomized, no placebo-controlled, phase Ⅰ/Ⅱ clinical trial assessing the safety and efficacy of intramuscular injection of autologous adipose tissue-derived mesenchymal stem cells in patients with severe Buerger’s disease. Cell Med, 2016, 9(3): 87-102.
8.	Xie B, Luo H, Zhang Y, et al. Autologous stem cell therapy in critical limb ischemia: a meta-analysis of randomized controlled trials. Stem Cells Int, 2018, 2018: 7528464.
9.	Wan J, Yang Y, Ma ZH, et al. Autologous peripheral blood stem cell transplantation to treat thromboangiitis obliterans: preliminary results. Eur Rev Med Pharmacol Sci, 2016, 20(3): 509-513.
10.	于靖宜, 李尚珠, 吳立華, 等. 自體外周血單個核細胞治療血栓閉塞性脈管炎重度下肢缺血的初步療效評價. 中國實驗血液學雜志, 2016, 24(3): 892-896.
11.	張濤, 萬華輝, 郭雪艷, 等. 自體外周血干細胞治療早期血栓閉塞性脈管炎的療效觀察. 陜西醫學雜志, 2014(4): 431-433.
12.	Guo J, Guo L, Cui S, et al. Autologous bone marrow-derived mononuclear cell therapy in Chinese patients with critical limb ischemia due to thromboangiitis obliterans: 10-year results. Stem Cell Res Ther, 2018, 9(1): 43.
13.	Heo SH, Park YS, Kang ES, et al. Early results of clinical application of autologous whole bone marrow stem cell transplantation for critical limb ischemia with Buerger’s disease. Sci Rep, 2016, 6: 19690.
14.	唐石晶, 郭發才, 湯敬東. 射頻消融、干細胞移植及藥物灌注治療血栓閉塞性脈管炎的有效性及安全性. 血管與腔內血管外科雜志, 2019, 5(2): 103-108.
15.	白超, 郭晨明, 羅軍. 自體骨髓干細胞移植治療血栓閉塞性脈管炎: 5 年隨訪. 中國組織工程研究, 2015(23): 3692-3697.
16.	Baran ?, Durdu S, ?z??nar E, et al. Long-term follow-up of patients with Buerger’s disease after autologous stem cell therapy. Anatol J Cardiol, 2019, 21(3): 155-162.
17.	Parikh PP, Liu ZJ, Velazquez OC. A molecular and clinical review of stem cell therapy in critical limb ischemia. Stem Cells Int, 2017: 3750829.
18.	Clayton ZE, Yuen GS, Sadeghipour S, et al. A comparison of the pro-angiogenic potential of human induced pluripotent stem cell derived endothelial cells and induced endothelial cells in a murine model of peripheral arterial disease. Int J Cardiol, 2017, 234: 81-89.
19.	Kim DH, Ko YG, Ahn CM, et al. Immediate and late outcomes of endovascular therapy for lower extremity arteries in Buerger disease. J Vasc Surg, 2018, 67(6): 1769-1777.
20.	Cooper LT, Tse TS, Mikhail MA, et al. Long-term survival and amputation risk in thromboangiitis obliterans (Buerger’s disease). J Am Coll Cardiol, 2004, 44(12): 2410-2411.
21.	Cacione DG, Macedo CR, Baptista-Silva JC. Pharmacological treatment for Buerger’s disease. Cochrane Database Syst Rev, 2016, 3: CD011033.
22.	Shapouri-Moghaddam A, Saeed Modaghegh MH, Rahimi HR, et al. Molecular mechanisms regulating immune responses in thromboangiitis obliterans: a comprehensive review. Iran J Basic Med Sci, 2019, 22(3): 215-224.
23.	Narváez J, García-Gómez C, álvarez L, et al. Efficacy of bosentan in patients with refractory thromboangiitis obliterans (Buerger disease): a case series and review of the literature. Medicine (Baltimore), 2016, 95(48): e5511.
24.	Chao TH, Tseng SY, Chen IC, et al. Cilostazol enhances mobilization and proliferation of endothelial progenitor cells and collateral formation by modifying vasculo-angiogenic biomarkers in peripheral arterial disease. Int J Cardiol, 2014, 172(2): e371-e374.
25.	Hemsinli D, Altun G, Kaplan ST, et al. Hyperbaric oxygen treatment in thromboangiitis obliterans: a retrospective clinical audit. Diving Hyperb Med, 2018, 48(1): 31-35.
26.	谷涌泉, 佟鑄, 郭連瑞. 干細胞移植治療下肢重度缺血. 中華普通外科學文獻 (電子版), 2015, 9(1): 8-10.
27.	杜俊文, 吳韜, 張坤, 等. 臍帶間充質干細胞聯合骨髓干細胞治療下肢缺血. 中國組織工程研究, 2017, 21(1): 82-86.
28.	周慧敏, 劉璠, 楊愛格, 等. 臍帶血單個核細胞移植治療對 2 型糖尿病下肢血管病變患者血清 VEGF 和 bFGF 的影響. 廣東醫學, 2015(19): 3021-3023.
29.	Hopman RK, DiPersio JF. Advances in stem cell mobilization. Blood Rev, 2014, 28(1): 31-40.
30.	Yang SS, Kim NR, Park KB, et al. A phase Ⅰ study of human cord blood-derived mesenchymal stem cell therapy in patients with peripheral arterial occlusive disease. Int J Stem Cells, 2013, 6(1): 37-44.
31.	劉璠, 周慧敏, 楊愛格, 等. 不同來源單個核細胞移植對 2 型糖尿病下肢血管病變的療效比較. 中華細胞與干細胞雜志 (電子版), 2016, 6(6): 351-355.
32.	Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng, 2001, 7(2): 211-228.
33.	中國醫藥生物技術協會皮膚軟組織修復與重建技術分會. 脂肪組織來源的干細胞提取、制備及儲存質量管理專家共識. 解放軍醫學雜志, 2018, 43(10): 811-815.
34.	Rathjen PD, Lake J, Whyatt LM, et al. Properties and uses of embryonic stem cells: prospects for application to human biology and gene therapy. Reprod Fertil Dev, 1998, 10(1): 31-47.
35.	孫英倫, 馬振桓, 楊鏞, 等. 對血栓閉塞性脈管炎患者截肢平面的研究. 中國現代醫學雜志, 2017, 27(15): 53-57.
36.	Aicher A, Heeschen C, Sasaki K, et al. Low-energy shock wave for enhancing recruitment of endothelial progenitor cells: a new modality to increase efficacy of cell therapy in chronic hind limb ischemia. Circulation, 2006, 114(25): 2823-2830.
37.	袁大江, 彭吾訓, 張飛, 等. 低濃度過氧化氫預處理增強骨髓間充質干細胞抗氧化應激損傷的能力. 中國組織工程研究, 2019, 23(13): 1982-1988.
38.	王倩, 劉羿, 張雨, 等. 低氧條件下人脂肪間充質干細胞分泌多種細胞因子的水平. 中國組織工程研究, 2019, 23(29): 4681-4687.
39.	Nowicki M, Wierzbowska A, Ma?achowski R, et al. VEGF, ANGPT1, ANGPT2, and MMP-9 expression in the autologous hematopoietic stem cell transplantation and its impact on the time to engraftment. Ann Hematol, 2017, 96(12): 2103-2112.
40.	Hsu MN, Chang YH, Truong VA, et al. CRISPR technologies for stem cell engineering and regenerative medicine. Biotechnol Adv, 2019, 37(8): 107447.
41.	閆波, 蘇少飛, 田玉峰, 等. 自體骨髓干細胞移植治療嚴重下肢缺血性疾病療效的影響因素分析. 中國血管外科雜志 (電子版), 2016, 8(2): 146-149.
42.	Jeon YJ, Kim J, Cho JH, et al. Comparative analysis of human mesenchymal stem cells derived from bone marrow, placenta, and adipose tissue as sources of cell therapy. J Cell Biochem, 2016, 117(5): 1112-1125.
43.	Chandra P, Lee SJ. Synthetic extracellular microenvironment for modulating stem cell behaviors. Biomark Insights, 2015, 10(Suppl 1): 105-116.
44.	Jiang YC, Wang XF, Xu YY, et al. Polycaprolactone nanofibers containing vascular endothelial growth factor-encapsulated gelatin particles enhance mesenchymal stem cell differentiation and angiogenesis of endothelial cells. Biomacromolecules, 2018, 19(9): 3747-3753.
45.	Sun L, Wu L, Qiao Z, et al. Analysis of possible factors relating to prognosis in autologous peripheral blood mononuclear cell transplantation for critical limb ischemia. Cytotherapy, 2014, 16(8): 1110-1116.
46.	Aoyama N, Nishinari M, Ohtani S, et al. Clinical features and predictors of patients with critical limb ischemia who responded to autologous mononuclear cell transplantation for therapeutic angiogenesis. Heart Vessels, 2017, 32(9): 1099-1108.
47.	Dash NR, Dash SN, Routray P, et al. Targeting nonhealing ulcers of lower extremity in human through autologous bone marrow-derived mesenchymal stem cells. Rejuvenation Res, 2009, 12(5): 359-366.

1. Folkman J. Therapeutic angiogenesis in ischemic limbs. Circulation, 1998, 97(12): 1108-1110.
2. Tateishi-Yuyama E, Matsubara H, Murohara T, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study anda randomised controlled trial. Lancet, 2002, 360(9331): 427-435.
3. 中華醫學會醫學工程學分會干細胞工程專業委員會, 中華醫學會外科學分會血管外科學組. 自體干細胞移植規范化治療下肢慢性缺血性疾病的專家共識. 中華細胞與干細胞雜志 (電子版), 2012, 2(1): 1-4.
4. Dong Z, Pan T, Fang Y, et al. Purified CD34⁺ cells versus peripheral blood mononuclear cells in the treatment of angiitis-induced no-option critical limb ischaemia: 12-month results of a prospective randomised single-blinded non-inferiority trial. EBioMedicine, 2018, 35: 46-57.
5. Fang Y, Wei Z, Chen B, et al. A five-year study of the efficacy of purified CD34⁺ cell therapy for angiitis-induced no-option critical limb ischemia. Stem Cells Transl Med, 2018, 7(8): 583-590.
6. Martin-Rufino JD, Lozano FS, Redondo AM, et al. Sequential intravenous allogeneic mesenchymal stromal cells as a potential treatment for thromboangiitis obliterans (Buerger’s disease). Stem Cell Res Ther, 2018, 9(1): 150.
7. Ra JC, Jeong EC, Kang SK, et al. A prospective, nonrandomized, no placebo-controlled, phase Ⅰ/Ⅱ clinical trial assessing the safety and efficacy of intramuscular injection of autologous adipose tissue-derived mesenchymal stem cells in patients with severe Buerger’s disease. Cell Med, 2016, 9(3): 87-102.
8. Xie B, Luo H, Zhang Y, et al. Autologous stem cell therapy in critical limb ischemia: a meta-analysis of randomized controlled trials. Stem Cells Int, 2018, 2018: 7528464.
9. Wan J, Yang Y, Ma ZH, et al. Autologous peripheral blood stem cell transplantation to treat thromboangiitis obliterans: preliminary results. Eur Rev Med Pharmacol Sci, 2016, 20(3): 509-513.
10. 于靖宜, 李尚珠, 吳立華, 等. 自體外周血單個核細胞治療血栓閉塞性脈管炎重度下肢缺血的初步療效評價. 中國實驗血液學雜志, 2016, 24(3): 892-896.
11. 張濤, 萬華輝, 郭雪艷, 等. 自體外周血干細胞治療早期血栓閉塞性脈管炎的療效觀察. 陜西醫學雜志, 2014(4): 431-433.
12. Guo J, Guo L, Cui S, et al. Autologous bone marrow-derived mononuclear cell therapy in Chinese patients with critical limb ischemia due to thromboangiitis obliterans: 10-year results. Stem Cell Res Ther, 2018, 9(1): 43.
13. Heo SH, Park YS, Kang ES, et al. Early results of clinical application of autologous whole bone marrow stem cell transplantation for critical limb ischemia with Buerger’s disease. Sci Rep, 2016, 6: 19690.
14. 唐石晶, 郭發才, 湯敬東. 射頻消融、干細胞移植及藥物灌注治療血栓閉塞性脈管炎的有效性及安全性. 血管與腔內血管外科雜志, 2019, 5(2): 103-108.
15. 白超, 郭晨明, 羅軍. 自體骨髓干細胞移植治療血栓閉塞性脈管炎: 5 年隨訪. 中國組織工程研究, 2015(23): 3692-3697.
16. Baran ?, Durdu S, ?z??nar E, et al. Long-term follow-up of patients with Buerger’s disease after autologous stem cell therapy. Anatol J Cardiol, 2019, 21(3): 155-162.
17. Parikh PP, Liu ZJ, Velazquez OC. A molecular and clinical review of stem cell therapy in critical limb ischemia. Stem Cells Int, 2017: 3750829.
18. Clayton ZE, Yuen GS, Sadeghipour S, et al. A comparison of the pro-angiogenic potential of human induced pluripotent stem cell derived endothelial cells and induced endothelial cells in a murine model of peripheral arterial disease. Int J Cardiol, 2017, 234: 81-89.
19. Kim DH, Ko YG, Ahn CM, et al. Immediate and late outcomes of endovascular therapy for lower extremity arteries in Buerger disease. J Vasc Surg, 2018, 67(6): 1769-1777.
20. Cooper LT, Tse TS, Mikhail MA, et al. Long-term survival and amputation risk in thromboangiitis obliterans (Buerger’s disease). J Am Coll Cardiol, 2004, 44(12): 2410-2411.
21. Cacione DG, Macedo CR, Baptista-Silva JC. Pharmacological treatment for Buerger’s disease. Cochrane Database Syst Rev, 2016, 3: CD011033.
22. Shapouri-Moghaddam A, Saeed Modaghegh MH, Rahimi HR, et al. Molecular mechanisms regulating immune responses in thromboangiitis obliterans: a comprehensive review. Iran J Basic Med Sci, 2019, 22(3): 215-224.
23. Narváez J, García-Gómez C, álvarez L, et al. Efficacy of bosentan in patients with refractory thromboangiitis obliterans (Buerger disease): a case series and review of the literature. Medicine (Baltimore), 2016, 95(48): e5511.
24. Chao TH, Tseng SY, Chen IC, et al. Cilostazol enhances mobilization and proliferation of endothelial progenitor cells and collateral formation by modifying vasculo-angiogenic biomarkers in peripheral arterial disease. Int J Cardiol, 2014, 172(2): e371-e374.
25. Hemsinli D, Altun G, Kaplan ST, et al. Hyperbaric oxygen treatment in thromboangiitis obliterans: a retrospective clinical audit. Diving Hyperb Med, 2018, 48(1): 31-35.
26. 谷涌泉, 佟鑄, 郭連瑞. 干細胞移植治療下肢重度缺血. 中華普通外科學文獻 (電子版), 2015, 9(1): 8-10.
27. 杜俊文, 吳韜, 張坤, 等. 臍帶間充質干細胞聯合骨髓干細胞治療下肢缺血. 中國組織工程研究, 2017, 21(1): 82-86.
28. 周慧敏, 劉璠, 楊愛格, 等. 臍帶血單個核細胞移植治療對 2 型糖尿病下肢血管病變患者血清 VEGF 和 bFGF 的影響. 廣東醫學, 2015(19): 3021-3023.
29. Hopman RK, DiPersio JF. Advances in stem cell mobilization. Blood Rev, 2014, 28(1): 31-40.
30. Yang SS, Kim NR, Park KB, et al. A phase Ⅰ study of human cord blood-derived mesenchymal stem cell therapy in patients with peripheral arterial occlusive disease. Int J Stem Cells, 2013, 6(1): 37-44.
31. 劉璠, 周慧敏, 楊愛格, 等. 不同來源單個核細胞移植對 2 型糖尿病下肢血管病變的療效比較. 中華細胞與干細胞雜志 (電子版), 2016, 6(6): 351-355.
32. Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng, 2001, 7(2): 211-228.
33. 中國醫藥生物技術協會皮膚軟組織修復與重建技術分會. 脂肪組織來源的干細胞提取、制備及儲存質量管理專家共識. 解放軍醫學雜志, 2018, 43(10): 811-815.
34. Rathjen PD, Lake J, Whyatt LM, et al. Properties and uses of embryonic stem cells: prospects for application to human biology and gene therapy. Reprod Fertil Dev, 1998, 10(1): 31-47.
35. 孫英倫, 馬振桓, 楊鏞, 等. 對血栓閉塞性脈管炎患者截肢平面的研究. 中國現代醫學雜志, 2017, 27(15): 53-57.
36. Aicher A, Heeschen C, Sasaki K, et al. Low-energy shock wave for enhancing recruitment of endothelial progenitor cells: a new modality to increase efficacy of cell therapy in chronic hind limb ischemia. Circulation, 2006, 114(25): 2823-2830.
37. 袁大江, 彭吾訓, 張飛, 等. 低濃度過氧化氫預處理增強骨髓間充質干細胞抗氧化應激損傷的能力. 中國組織工程研究, 2019, 23(13): 1982-1988.
38. 王倩, 劉羿, 張雨, 等. 低氧條件下人脂肪間充質干細胞分泌多種細胞因子的水平. 中國組織工程研究, 2019, 23(29): 4681-4687.
39. Nowicki M, Wierzbowska A, Ma?achowski R, et al. VEGF, ANGPT1, ANGPT2, and MMP-9 expression in the autologous hematopoietic stem cell transplantation and its impact on the time to engraftment. Ann Hematol, 2017, 96(12): 2103-2112.
40. Hsu MN, Chang YH, Truong VA, et al. CRISPR technologies for stem cell engineering and regenerative medicine. Biotechnol Adv, 2019, 37(8): 107447.
41. 閆波, 蘇少飛, 田玉峰, 等. 自體骨髓干細胞移植治療嚴重下肢缺血性疾病療效的影響因素分析. 中國血管外科雜志 (電子版), 2016, 8(2): 146-149.
42. Jeon YJ, Kim J, Cho JH, et al. Comparative analysis of human mesenchymal stem cells derived from bone marrow, placenta, and adipose tissue as sources of cell therapy. J Cell Biochem, 2016, 117(5): 1112-1125.
43. Chandra P, Lee SJ. Synthetic extracellular microenvironment for modulating stem cell behaviors. Biomark Insights, 2015, 10(Suppl 1): 105-116.
44. Jiang YC, Wang XF, Xu YY, et al. Polycaprolactone nanofibers containing vascular endothelial growth factor-encapsulated gelatin particles enhance mesenchymal stem cell differentiation and angiogenesis of endothelial cells. Biomacromolecules, 2018, 19(9): 3747-3753.
45. Sun L, Wu L, Qiao Z, et al. Analysis of possible factors relating to prognosis in autologous peripheral blood mononuclear cell transplantation for critical limb ischemia. Cytotherapy, 2014, 16(8): 1110-1116.
46. Aoyama N, Nishinari M, Ohtani S, et al. Clinical features and predictors of patients with critical limb ischemia who responded to autologous mononuclear cell transplantation for therapeutic angiogenesis. Heart Vessels, 2017, 32(9): 1099-1108.
47. Dash NR, Dash SN, Routray P, et al. Targeting nonhealing ulcers of lower extremity in human through autologous bone marrow-derived mesenchymal stem cells. Rejuvenation Res, 2009, 12(5): 359-366.

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