脂肪源性干細胞臨床轉化應用中的相關問題_《中國修復重建外科雜志》

作者：

劉宏偉 ¹ , 程飚 ² , 付小兵 ³

1暨南大學附屬第一醫院整形外科再生醫學教育部重點實驗室（廣州，510630）;;
2 廣州軍區廣州總醫院整形外科全軍熱區損傷救治與組織修復重點實驗室;;
3 解放軍總醫院第一附屬醫院全軍創傷修復重點實驗室;

關鍵詞：

脂肪源性干細胞基質血管成分細胞轉化醫學再生醫學

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目的對近年來國內外有關脂肪源性干細胞（adipose-derived stem cells，ASCs）在臨床轉化應用中應該或必須關注的問題進行綜述。方法廣泛查閱近年相關文獻，對ASCs生產和使用過程中有關產品的管理、生產、運輸、使用、安全性等方面進行綜合分析。結果ASCs作為成體干細胞家族的新成員在再生醫學領域展現了廣闊的應用前景。目前在美國國立衛生研究院（NIH）的http: //www.clinicaltrials.gov網站上已注冊登記的在15個國家進行的臨床試驗達40多個，說明世界范圍內從事干細胞研究和應用的學者對ASCs臨床轉化應用的濃厚興趣和重視。在臨床轉化應用中，ASCs產品存在管理，生產應遵循的質量控制標準，病原微生物污染的預防措施，分離過程中對酶和相關試劑的要求，取材過程中供區、年齡和性別可能的影響，低溫貯藏，產品運輸以及安全性等一系列問題。結論ASCs作為成體干細胞具有較好的臨床轉化應用優點，在臨床應用中對其存在的問題必須給予高度重視和進一步研究，以加速其臨床轉化過程。

引用本文： 劉宏偉,程飚,付小兵. 脂肪源性干細胞臨床轉化應用中的相關問題. 中國修復重建外科雜志, 2012, 26(10): 1242-1246. doi: 復制

1.	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.
2.	Gimble JM, Bunnell BA, Guilak F. Human adipose-derived cells: an update on the transition to clinical translation. Regen Med, 2012, 7(2): 225-235.
3.	Gimble JM, Bunnell BA, Chiu ES, et al. Concise review: Adipose-derived stromal vascular fraction cells and stem cells: let’s not get lost in translation. Stem Cells, 2011, 29(5): 749-754.
4.	Sensebé L, Bourin P, Tarte K. Good manufacturing practices production of mesenchymal stem/stromal cells. Hum Gene Ther, 2011, 22(1): 19-26.
5.	Lin K, Matsubara Y, Masuda Y, et al. Characterization of adipose tissue-derived cells isolated with the Celution system. Cytotherapy, 2008, 10(4): 417-426.
6.	Güven S, Karagianni M, Schwalbe M, et al. Validation of an automated procedure to isolate human adipose tissue-derived cells by using the Sepax? technology. Tissue Eng Part C Methods, 2012. [Epub ahead of print].
7.	黃海玲, 劉宏偉, 佘文莉, 等. 介紹一種微創無菌快速獲取可移植脂肪顆粒裝置. 中華整形外科雜志, 2011, 27(6): 467-468.
8.	Doi K, Tanaka S, Iida H, et al. Stromal vascular fraction isolated from lipo-aspirates using an automated processing system: bench and bed analysis. J Tissue Eng Regen Med, 2012. [Epub ahead of print].
9.	Yoshimura K, Shigeura T, Matsumoto D, et al. Characterization of freshly isolated and cultured cells derived from the fatty and fluid portion of liposuction aspirates. J Cell Physiol, 2006, 208(1): 64-76.
10.	Lindroos B, Aho KL, Kuokkanen H, et al. Differential gene expression in adipose stem cells cultured in allogeneic human serum versus fetal bovine serum. Tissue Eng Part A, 2010, 16(7): 2281-2294.
11.	王太平, 徐國彤, 周琪, 等. 國際干細胞研究學會《干細胞臨床轉化指南》. 生命科學, 2009, 21(5): 747-756.
12.	Fink T, Rasmussen JG, Lund P, et al. Isolation and expansion of adipose-derived stem cells for tissue engineering. Front Biosci (Elite Ed), 2011, 3: 256-263.
13.	van Harmelen V, Skurk T, Röhrig K, et al. Effect of BMI and age on adipose tissue cellularity and differentiation capacity in women. Int J Obes Relat Metab Disord, 2003, 27(8): 889-895.
14.	Mojallal A, Lequeux C, Shipkov C, et al. Influence of age and body mass index on the yield and proliferation capacity of adipose-derived stem cells. Aesthetic Plast Surg, 2011, 35(6): 1097-1105.
15.	Ogawa R, Mizuno H, Watanabe A, et al. Adipogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice-including relationship of sex differences. Biochem Biophys Res Commun, 2004, 319(2): 511-517.
16.	Aksu AE, Rubin JP, Dudas JR, et al. Role of gender and anatomical region on induction of osteogenic differentiation of human adipose-derived stem cells. Ann Plast Surg, 2008, 60(3): 306-322.
17.	Chen HT, Lee MJ, Chen CH, et al. Proliferation and differentiation potential of human adipose-derived mesenchymal stem cells isolated from elderly patients with osteoporotic fractures. J Cell Mol Med, 2012, 16(3): 582-593.
18.	Shu W, Shu YT, Yundai C, et al. Comparing the biological characteristics of adipose tissue-derived stem cells of different persons. J Cell Biochem, 2012, 113(6): 2020-2026.
19.	Alt EU, Senst C, Murthy SN, et al. Aging alters tissue resident mesenchymal stem cell properties. Stem Cell Res, 2012, 8(2): 215-225.
20.	Sowa Y, Imura T, Numajiri T, et al. Adipose-derived stem cells produce factors enhancing peripheral nerve regeneration: influence of age and anatomic site of origin. Stem Cells Dev, 2012, 21(11): 1852-1862.
21.	陳燕, 陸志剛, 白海, 等. 細胞內外海藻糖對紅細胞冰凍干燥保存的影響. 中國輸血雜志, 2012, 25(3): 236-239.
22.	劉廣鵬, 李宇琳, 孫劍, 等. 低溫凍存對人脂肪來源干細胞成骨能力影響的實驗研究. 中國修復重建外科雜志, 2010, 24(10): 1224-1227.
23.	Feng Z, Ting J, Alfonso Z, et al. Fresh and cryopreserved, uncultured adipose tissue-derived stem and regenerative cells ameliorate ischemia-reperfusion-induced acute kidney injury. Nephrol Dial Transplant, 2010, 25(12): 3874-3884.
24.	Lee JE, Kim I, Kim M. Adipogenic differentiation of human adipose tissue-derived stem cells obtained from cryopreserved adipose aspirates. Dermatol Surg, 2010, 36(7): 1078-1083.
25.	Martinello T, Bronzini I, Maccatrozzo L, et al. Canine adipose-derived-mesenchymal stem cells do not lose stem features after a long-term cryopreservation. Res Vet Sci, 2011, 91(1): 18-24.
26.	James AW, Levi B, Nelson ER, et al. Deleterious effects of freezing on osteogenic differentiation of human adipose-derived stromal cells in vitro and in vivo. Stem Cells Dev, 2011, 20(3): 427-439.
27.	Matsumoto D, Shigeura T, Sato K, et al. Influences of preservation at various temperatures on liposuction aspirates. Plast Reconstr Surg, 2007, 120(6): 1510-1517.
28.	Prockop DJ, Brenner M, Fibbe WE, et al. Defining the risks of mesenchymal stromal cell therapy. Cytotherapy, 2010, 12(5): 576-578.
29.	Ra JC, Kang SK, Shin IS, et al. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells. J Transl Med, 2011, 9: 181.
30.	López-Iglesias P, Blázquez-Martínez A, Fernández-Delgado J, et al. Short and long term fate of human AMSC subcutaneously injected in mice. World J Stem Cells, 2011, 3(6): 53-62.
31.	Sun B, Roh KH, Park JR, et al. Therapeutic potential of mesenchymal stromal cells in a mouse breast cancer metastasis model. Cytotherapy, 2009, 11(3): 289-298.
32.	Pinilla S, Alt E, Abdul Khalek FJ, et al. Tissue resident stem cells produce CCL5 under the influence of cancer cells and thereby promote breast cancer cell invasion. Cancer Lett, 2009, 284(1): 80-85.
33.	Zimmerlin L, Donnenberg AD, Rubin JP, et al. Regenerative therapy and cancer: in vitro and in vivo studies of the interaction between adipose-derived stem cells and breast cancer cells from clinical isolates. Tissue Eng Part A, 2011, 17(1-2): 93-106.
34.	Muehlberg FL, Song YH, Krohn A, et al. Tissue-resident stem cells promote breast cancer growth and metastasis. Carcinogenesis, 2009, 30(4): 589-597.
35.	Donnenberg VS, Zimmerlin L, Rubin JP, et al. Regenerative therapy after cancer: what are the risks? Tissue Eng Part B Rev, 2010, 16(6): 567-575.

1. 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.
2. Gimble JM, Bunnell BA, Guilak F. Human adipose-derived cells: an update on the transition to clinical translation. Regen Med, 2012, 7(2): 225-235.
3. Gimble JM, Bunnell BA, Chiu ES, et al. Concise review: Adipose-derived stromal vascular fraction cells and stem cells: let’s not get lost in translation. Stem Cells, 2011, 29(5): 749-754.
4. Sensebé L, Bourin P, Tarte K. Good manufacturing practices production of mesenchymal stem/stromal cells. Hum Gene Ther, 2011, 22(1): 19-26.
5. Lin K, Matsubara Y, Masuda Y, et al. Characterization of adipose tissue-derived cells isolated with the Celution system. Cytotherapy, 2008, 10(4): 417-426.
6. Güven S, Karagianni M, Schwalbe M, et al. Validation of an automated procedure to isolate human adipose tissue-derived cells by using the Sepax? technology. Tissue Eng Part C Methods, 2012. [Epub ahead of print].
7. 黃海玲, 劉宏偉, 佘文莉, 等. 介紹一種微創無菌快速獲取可移植脂肪顆粒裝置. 中華整形外科雜志, 2011, 27(6): 467-468.
8. Doi K, Tanaka S, Iida H, et al. Stromal vascular fraction isolated from lipo-aspirates using an automated processing system: bench and bed analysis. J Tissue Eng Regen Med, 2012. [Epub ahead of print].
9. Yoshimura K, Shigeura T, Matsumoto D, et al. Characterization of freshly isolated and cultured cells derived from the fatty and fluid portion of liposuction aspirates. J Cell Physiol, 2006, 208(1): 64-76.
10. Lindroos B, Aho KL, Kuokkanen H, et al. Differential gene expression in adipose stem cells cultured in allogeneic human serum versus fetal bovine serum. Tissue Eng Part A, 2010, 16(7): 2281-2294.
11. 王太平, 徐國彤, 周琪, 等. 國際干細胞研究學會《干細胞臨床轉化指南》. 生命科學, 2009, 21(5): 747-756.
12. Fink T, Rasmussen JG, Lund P, et al. Isolation and expansion of adipose-derived stem cells for tissue engineering. Front Biosci (Elite Ed), 2011, 3: 256-263.
13. van Harmelen V, Skurk T, Röhrig K, et al. Effect of BMI and age on adipose tissue cellularity and differentiation capacity in women. Int J Obes Relat Metab Disord, 2003, 27(8): 889-895.
14. Mojallal A, Lequeux C, Shipkov C, et al. Influence of age and body mass index on the yield and proliferation capacity of adipose-derived stem cells. Aesthetic Plast Surg, 2011, 35(6): 1097-1105.
15. Ogawa R, Mizuno H, Watanabe A, et al. Adipogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice-including relationship of sex differences. Biochem Biophys Res Commun, 2004, 319(2): 511-517.
16. Aksu AE, Rubin JP, Dudas JR, et al. Role of gender and anatomical region on induction of osteogenic differentiation of human adipose-derived stem cells. Ann Plast Surg, 2008, 60(3): 306-322.
17. Chen HT, Lee MJ, Chen CH, et al. Proliferation and differentiation potential of human adipose-derived mesenchymal stem cells isolated from elderly patients with osteoporotic fractures. J Cell Mol Med, 2012, 16(3): 582-593.
18. Shu W, Shu YT, Yundai C, et al. Comparing the biological characteristics of adipose tissue-derived stem cells of different persons. J Cell Biochem, 2012, 113(6): 2020-2026.
19. Alt EU, Senst C, Murthy SN, et al. Aging alters tissue resident mesenchymal stem cell properties. Stem Cell Res, 2012, 8(2): 215-225.
20. Sowa Y, Imura T, Numajiri T, et al. Adipose-derived stem cells produce factors enhancing peripheral nerve regeneration: influence of age and anatomic site of origin. Stem Cells Dev, 2012, 21(11): 1852-1862.
21. 陳燕, 陸志剛, 白海, 等. 細胞內外海藻糖對紅細胞冰凍干燥保存的影響. 中國輸血雜志, 2012, 25(3): 236-239.
22. 劉廣鵬, 李宇琳, 孫劍, 等. 低溫凍存對人脂肪來源干細胞成骨能力影響的實驗研究. 中國修復重建外科雜志, 2010, 24(10): 1224-1227.
23. Feng Z, Ting J, Alfonso Z, et al. Fresh and cryopreserved, uncultured adipose tissue-derived stem and regenerative cells ameliorate ischemia-reperfusion-induced acute kidney injury. Nephrol Dial Transplant, 2010, 25(12): 3874-3884.
24. Lee JE, Kim I, Kim M. Adipogenic differentiation of human adipose tissue-derived stem cells obtained from cryopreserved adipose aspirates. Dermatol Surg, 2010, 36(7): 1078-1083.
25. Martinello T, Bronzini I, Maccatrozzo L, et al. Canine adipose-derived-mesenchymal stem cells do not lose stem features after a long-term cryopreservation. Res Vet Sci, 2011, 91(1): 18-24.
26. James AW, Levi B, Nelson ER, et al. Deleterious effects of freezing on osteogenic differentiation of human adipose-derived stromal cells in vitro and in vivo. Stem Cells Dev, 2011, 20(3): 427-439.
27. Matsumoto D, Shigeura T, Sato K, et al. Influences of preservation at various temperatures on liposuction aspirates. Plast Reconstr Surg, 2007, 120(6): 1510-1517.
28. Prockop DJ, Brenner M, Fibbe WE, et al. Defining the risks of mesenchymal stromal cell therapy. Cytotherapy, 2010, 12(5): 576-578.
29. Ra JC, Kang SK, Shin IS, et al. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells. J Transl Med, 2011, 9: 181.
30. López-Iglesias P, Blázquez-Martínez A, Fernández-Delgado J, et al. Short and long term fate of human AMSC subcutaneously injected in mice. World J Stem Cells, 2011, 3(6): 53-62.
31. Sun B, Roh KH, Park JR, et al. Therapeutic potential of mesenchymal stromal cells in a mouse breast cancer metastasis model. Cytotherapy, 2009, 11(3): 289-298.
32. Pinilla S, Alt E, Abdul Khalek FJ, et al. Tissue resident stem cells produce CCL5 under the influence of cancer cells and thereby promote breast cancer cell invasion. Cancer Lett, 2009, 284(1): 80-85.
33. Zimmerlin L, Donnenberg AD, Rubin JP, et al. Regenerative therapy and cancer: in vitro and in vivo studies of the interaction between adipose-derived stem cells and breast cancer cells from clinical isolates. Tissue Eng Part A, 2011, 17(1-2): 93-106.
34. Muehlberg FL, Song YH, Krohn A, et al. Tissue-resident stem cells promote breast cancer growth and metastasis. Carcinogenesis, 2009, 30(4): 589-597.
35. Donnenberg VS, Zimmerlin L, Rubin JP, et al. Regenerative therapy after cancer: what are the risks? Tissue Eng Part B Rev, 2010, 16(6): 567-575.

《中國修復重建外科雜志》

脂肪源性干細胞臨床轉化應用中的相關問題

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《中國修復重建外科雜志》

脂肪源性干細胞臨床轉化應用中的相關問題

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料