• 1暨南大學(xué)附屬第一醫(yī)院整形外科 再生醫(yī)學(xué)教育部重點(diǎn)實(shí)驗(yàn)室（廣州，510630）;;
  • 2 廣州軍區(qū)廣州總醫(yī)院整形外科 全軍熱區(qū)損傷救治與組織修復(fù)重點(diǎn)實(shí)驗(yàn)室;;
  • 3 解放軍總醫(yī)院第一附屬醫(yī)院全軍創(chuàng)傷修復(fù)重點(diǎn)實(shí)驗(yàn)室;

目的 對(duì)近年來(lái)國(guó)內(nèi)外有關(guān)脂肪源性干細(xì)胞（adipose-derived stem cells，ASCs）在臨床轉(zhuǎn)化應(yīng)用中應(yīng)該或必須關(guān)注的問(wèn)題進(jìn)行綜述。 方法廣泛查閱近年相關(guān)文獻(xiàn)，對(duì)ASCs生產(chǎn)和使用過(guò)程中有關(guān)產(chǎn)品的管理、生產(chǎn)、運(yùn)輸、使用、安全性等方面進(jìn)行綜合分析。 結(jié)果ASCs作為成體干細(xì)胞家族的新成員在再生醫(yī)學(xué)領(lǐng)域展現(xiàn)了廣闊的應(yīng)用前景。目前在美國(guó)國(guó)立衛(wèi)生研究院（NIH）的http: //www.clinicaltrials.gov網(wǎng)站上已注冊(cè)登記的在15個(gè)國(guó)家進(jìn)行的臨床試驗(yàn)達(dá)40多個(gè)，說(shuō)明世界范圍內(nèi)從事干細(xì)胞研究和應(yīng)用的學(xué)者對(duì)ASCs臨床轉(zhuǎn)化應(yīng)用的濃厚興趣和重視。在臨床轉(zhuǎn)化應(yīng)用中，ASCs產(chǎn)品存在管理，生產(chǎn)應(yīng)遵循的質(zhì)量控制標(biāo)準(zhǔn)，病原微生物污染的預(yù)防措施，分離過(guò)程中對(duì)酶和相關(guān)試劑的要求，取材過(guò)程中供區(qū)、年齡和性別可能的影響，低溫貯藏，產(chǎn)品運(yùn)輸以及安全性等一系列問(wèn)題。 結(jié)論ASCs作為成體干細(xì)胞具有較好的臨床轉(zhuǎn)化應(yīng)用優(yōu)點(diǎn)，在臨床應(yīng)用中對(duì)其存在的問(wèn)題必須給予高度重視和進(jìn)一步研究，以加速其臨床轉(zhuǎn)化過(guò)程。

引用本文： 劉宏偉,程飚,付小兵. 脂肪源性干細(xì)胞臨床轉(zhuǎn)化應(yīng)用中的相關(guān)問(wèn)題. 中國(guó)修復(fù)重建外科雜志, 2012, 26(10): 1242-1246. doi: 復(fù)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(chuàng)無(wú)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(guó)彤, 周琪, 等. 國(guó)際干細(xì)胞研究學(xué)會(huì)《干細(xì)胞臨床轉(zhuǎn)化指南》. 生命科學(xué), 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(xì)胞內(nèi)外海藻糖對(duì)紅細(xì)胞冰凍干燥保存的影響. 中國(guó)輸血雜志, 2012, 25(3): 236-239.
22. 劉廣鵬, 李宇琳, 孫劍, 等. 低溫凍存對(duì)人脂肪來(lái)源干細(xì)胞成骨能力影響的實(shí)驗(yàn)研究. 中國(guó)修復(fù)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. 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. 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. 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. 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. 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. 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. 7. 黃海玲, 劉宏偉, 佘文莉, 等. 介紹一種微創(chuàng)無(wú)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. 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. 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. 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. 11. 王太平, 徐國(guó)彤, 周琪, 等. 國(guó)際干細(xì)胞研究學(xué)會(huì)《干細(xì)胞臨床轉(zhuǎn)化指南》. 生命科學(xué), 2009, 21(5): 747-756.
  12. 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. 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. 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. 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. 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. 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. 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. 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. 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. 21. 陳燕, 陸志剛, 白海, 等. 細(xì)胞內(nèi)外海藻糖對(duì)紅細(xì)胞冰凍干燥保存的影響. 中國(guó)輸血雜志, 2012, 25(3): 236-239.
  22. 22. 劉廣鵬, 李宇琳, 孫劍, 等. 低溫凍存對(duì)人脂肪來(lái)源干細(xì)胞成骨能力影響的實(shí)驗(yàn)研究. 中國(guó)修復(fù)重建外科雜志, 2010, 24(10): 1224-1227.
  23. 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. 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. 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. 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. 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. 28. Prockop DJ, Brenner M, Fibbe WE, et al. Defining the risks of mesenchymal stromal cell therapy. Cytotherapy, 2010, 12(5): 576-578.
  29. 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. 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. 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. 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. 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. 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. 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.