Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2015, vol. 24, nr 3, May-June, p. 545–548

doi: 10.17219/acem/31673

Publication type: review

Language: English

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Adipose Tissue-Derived Stem Cell Therapy for Post-Surgical Breast Reconstruction – More Light than Shadows

Alessandra Bielli1,A, Maria G. Scioli1,D, Pietro Gentile2,D, Valerio Cervelli2,E, Augusto Orlandi1,D,E

1 Department of Biomedicine and Prevention, Anatomic Pathology, University of Rome Tor Vergata, Italy

2 Department of Biomedicine and Prevention, Plastic Surgery, University of Rome Tor Vergata, Italy


Breast cancer remains the most common tumor in women, and new techniques for postsurgical breast reconstruction have been recently introduced. These new procedures include autologous fat grafting with or without the enrichment with autologous stromal vascular fraction (SVF), platelet-derived growth factors and insulin. The reported improvement of fat graft viability with these techniques likely depends on the presence in the SVF of multipotent resident adipose derived-stem cells (ASCs). The clinical advantage derives from the plasticity of ASCs and their ability to generate new functional adipose tissue and vessels. However, there is an ongoing debate regarding the possible interplay between breast tumor cells and resident or transplanted ASCs for their capacity to locally secrete growth factors. Most of the data in the literature concerning ASCs is derived from in vitro models, whereas the knowledge of ASC behavior in vivo remains scarce. Recent reports concerning SVF/ASC enrichment of fat graft did not describe any significant worsening of prognosis for patients undergoing those procedures. However, further studies and longer follow-ups are needed to specifically define technical procedures and to confirm the safety of procedures of SVF/ASC enrichment during post-surgical breast reconstruction.

Key words

ASCs, breast reconstruction, fat grafting, SVF.

References (32)

  1. Bostwick J 3rd: Breast reconstruction following mastectomy. CA Cancer J Clin 1995, 45, 289–304.
  2. Missana MC, Laurent I, Barreau L, Balleyguier C: Autologous fat transfer in reconstructive breast surgery: indications, technique and results. Eur J Surg Oncol 2007, 33, 685–690.
  3. Weichman KE, Broer PN, Tanna N, Wilson SC, Allan A, Levine JP, Ahn C, Choi M, Karp NS, Allen R: The role of autologous fat grafting in secondary microsurgical breast reconstruction. Ann Plast Surg 2013, 71, 24–30.
  4. Cervelli V, Gentile P, Scioli MG, Grimaldi M, Casciani CU, Spagnoli LG: Application of platelet-rich plasma in plastic surgery: clinical and in vitro evaluation. Tissue Eng Part C Methods 2009, 15, 625–634.
  5. Mitchell JB, McIntosh K, Zvonic S, Garrett S, Floyd ZE, Kloster A: Immunophenotype of human adipose-derived cells: Temporal changes in stromal-associated and stem cell-associated markers. Stem Cells 2006, 24, 376–385.
  6. Cervelli V, Scioli MG, Gentile P, Doldo E, Bonanno E, Spagnoli LG: Platelet-rich plasma greatly potentiates insulin-induced adipogenic differentiation of human adipose-derived stem cells through a serine/threonine kinase Akt-dependent mechanism and promotes clinical fat graft maintenance. Stem Cells Transl Med 2012, 1, 206–220.
  7. Gentile P, Orlandi A, Scioli MG, Di Pasquali C, Bocchini I, Curcio CB: Comparative translational study: the combined use of enhanced stromal vascular fraction and platelet-rich plasma improves fat grafting maintenance in breast reconstruction. Stem Cells Transl Med 2012, 1, 341–351.
  8. Gentile P, Di Pasquali C, Bocchini I, Floris M, Eleonora T, Fiaschetti V, Floris R, Cervelli V: Breast reconstruction with autologous fat graft mixed with platelet-rich plasma. Surg Innov 2013, 20, 370–376.
  9. Kolle SF, Fischer-Nielsen A, Mathiasen AB, Elberg JJ, Oliveri, RS, Glovinski PV: Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-controlled trial. Lancet 2013, 382, 1113–1120.
  10. Cervelli V, Gentile P, De Angelis B, Calabrese C, Di Stefani A, Scioli MG: Application of enhanced stromal vascular fraction and fat grafting mixed with PRP in post-traumatic lower extremity ulcers. Stem Cell Res 2011, 6, 103–111.
  11. Orlandi A, Bennett M: Progenitor cell-derived smooth muscle cells in vascular disease. Biochem Pharmacol 2010, 79, 1706–1713.
  12. Ferlosio A, Arcuri G, Doldo E, Scioli MG, De Falco S, Spagnoli LG: Age related increase of stem marker expression influences vascular smooth muscle cell properties. Atherosclerosis 2012, 224, 51–57.
  13. Stasi MA, Scioli MG, Arcuri G, Mattera GG, Lombardo K, Marcellini M, Riccioni T, De Falco S, Pisano C, Spagnoli LG, Borsini F, Orlandi A: Propionyl-L-carnitine improves postischemic blood flow recovery and arteriogenetic revascularization and reduces endothelial NADPH-oxidase 4-mediated superoxide production. Arterioscler Thromb Vasc Biol 2010, 30, 426–435.
  14. Rietjens M, De Lorenzi F, Rossetto F, Brenelli F, Manconi A, Martella S: Safety of fat grafting in secondary breast reconstruction after cancer. J Plast Reconstr Aesthet Surg 2011, 64, 477–483.
  15. Kucerova L, Skolekova S, Matuskova M, Bohac M, Kozovska Z: Altered features and increased chemosensitivity of human breast cancer cells mediated by adipose tissue-derived mesenchymal stromal cells. BMC Cancer 2013, 13, 535.
  16. Cassinelli G, Zuco V, Petrangolini G, De Cesare M, Tortoreto M, Lanzi C: The curative efficacy of namitecan (ST1968) in preclinical models of pediatric sarcoma is associated with antiangiogenic effects. Biochem Pharmacol 2012, 84, 163–171.
  17. Tarallo V, Vesci L, Capasso O, Esposito MT, Riccioni T, Pastore L, Orlandi A, Pisano C, De Falco S: A placental growth factor variant unable to recognize vascular endothelial growth factor (VEGF) receptor-1 inhibits VEGFdependent tumor angiogenesis via heterodimerization. Cancer Res 2010, 70, 3413.
  18. Gehmert S, Gehmert S, Prantl L, Vykoukal J, Alt E, Song YH: Breast cancer cells attract the migration of adipose tissue-derived stem cells via the PDGF-BB/PDGFR-b signaling pathway. Biochem Bioph Res Co 2010, 398, 601–605.
  19. Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R: Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis through Elevated SDF-1/CXCL12 Secretion. Cell 2005, 121, 335–348.
  20. Orlandi A, Bochaton-Piallat ML, Gabbiani G, Spagnoli LG: Aging, smooth muscle cells and vascular pathobiology: implications for atherosclerosis. Atherosclerosis 2006, 188, 221–230.
  21. De Wever O, Demetter P, Mareel M, Bracke M: Stromal myofibroblasts are drivers of invasive cancer growth. Int J Cancer 2008, 123, 2229–2238.
  22. Orlandi A, Bianchi L, Spagnoli LG: Myxoid dermatofibrosarcoma protuberans: morphological, ultrastructural and immunohistochemical features. J Cutan Pathol 199825, 386–393.
  23. Muehlberg FL, Song YH, Alexander K, Pinilla SP, Droll LH, Leng X: Tissue-resident stem cells promote breast cancer growth and metastasis. Carcinogenesis 2009, 30, 589–597.
  24. Wang YY, Lehuédé C, Laurent V, Dirat B, Dauvillier S, Bochet L: Adipose tissue and breast epithelial cells: a dangerous dynamic duo in breast cancer. Cancer Lett 2012, 324,142–151.
  25. Chandler EM, Seo BR, Califano JP, Andresen Eguiluz RC, Lee JS, Yoon CJ: Implanted adipose progenitor cells as physicochemical regulators of breast cancer. Proc Natl Acad Sci 2012, 109, 9786–9791.
  26. Orlandi A, Ciucci A, Ferlosio A, Pellegrino A, Chiariello L, Spagnoli LG: Increased expression and activity of matrix metalloproteinases characterize embolic cardiac myxomas. Am J Pathol 2005, 166, 1619–1628.
  27. Park TS, Donnenberg VS, Donnenberg AD, Zambidis ET, Zimmerlin L: Dynamic interaction between cancer stem cells and their stromal patners. Curr Pathobiol Rep 2014, 2, 42–52.
  28. Dirat B, Bochet L, Dabek M, Daviaud D, Dauvillier S, Majed B: Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res 2011, 71, 2455–2465.
  29. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW: Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 2007, 449, 557–563.
  30. Pinilla S, Alt E, Abdul Khalek FJ, Jotzu C, Muehlberg F, Beckmann C: Tissue resident stem cells produce CCL5 under the influence of cancer cells and thereby promote breast cancer cell invasion. Cancer Letters 2009, 284, 80–85.
  31. Zimmerlin L, Donnenberg AD, Rubin JP, Basse P, Landreneau RJ, Donnenberg VS: 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, 93–106.
  32. Sun B, Roh KH, Park JR, Lee SR, Park SB, Jung JW: Therapeutic potential of mesenchymal stromal cells in a mouse breast cancer metastasis model. Cytotherapy 2009, 11, 289–298.