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Effects of Stromal Vascular Fraction on Breast Cancer Growth and Fat Engraftment in NOD/SCID Mice

  • Joon Seok Lee
  • PilSeon Eo
  • Min Chul Kim
  • Jae Bong Kim
  • Hee Kyung Jin
  • Jae-Sung Bae
  • Jae-hwan Jeong
  • Ho Yong Park
  • Jung Dug YangEmail author
Original Article Basic Science/Experimental
  • 36 Downloads

Abstract

Background

To overcome unpredictable fat graft resorption, cell-assisted lipotransfer using stromal vascular fraction (SVF) has been introduced. However, its effect on cancer growth stimulation and its oncological safety are debatable. We investigated the effect of SVF on adjacent breast cancer and transplanted fat in a mouse model.

Methods

A breast cancer xenograft model was constructed by injecting 2 × 106 MDA-MB-231-luc breast cancer cells into the right lower back of 40 NOD/SCID mice. Two weeks later, cancer size was sorted according to signal density using an in vivo optical imaging system, and 36 mice were included. Human fat was extracted from the abdomen, and SVFs were isolated using a component isolator. The mice were divided into four groups: A, controls; B, injected with 30 μl SVF; C, injected with 0.5 ml fat and 30 μl saline; group D, injected with 0.5 ml fat and 30 μl SVF. Magnetic resonance imaging and three-dimensional micro-computed tomography volumetric analysis were performed at 4 and 8 weeks.

Results

Tumor volume was 43.6, 42.3, 48.7, and 42.4 mm3 at the initial time point and 6780, 5940, 6080, and 5570 mm3 at 8 weeks in groups A, B, C, and D, respectively. Fat graft survival volume after 8 weeks was 49.32% and 62.03% in groups C and D, respectively. At 2-month follow-up after fat grafting in the xenograft model, SVF injection showed an increased fat survival rate and did not increase the adjacent tumor growth significantly.

Conclusion

Fat grafting with SVF yields satisfactory outcome in patients who undergo breast reconstruction surgery.

No Level Assigned

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Keywords

Stromal vascular fraction Breast cancer Fat graft Fat injection 

Notes

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have not conflicts of interest related to the manuscript.

Human and Animal Rights Statement

This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The animal experiment was conducted after review and obtaining approval from the Institutional Animal Care and Use Committee of Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF) (approval number: DGMIF-17021401-00).

Informed Consent

For this type of study, informed consent is not required.

References

  1. 1.
    Coleman SR (1997) Facial recontouring with lipostructure. Clin Plast Surg 24:347–367Google Scholar
  2. 2.
    Coleman SR (2002) Hand rejuvenation with structural fat grafting. Plast Reconstr Surg 110:1731–1744CrossRefGoogle Scholar
  3. 3.
    Gatti JE (1999) Permanent lip augmentation with serial fat grafting. Ann Plast Surg 42:376–380CrossRefGoogle Scholar
  4. 4.
    Guerrerosantos J (1996) Autologous fat grafting for body contouring. Clin Plast Surg 23:619–631Google Scholar
  5. 5.
    Roberts TL 3rd, Weinfeld AB, Bruner TW, Nguyen K (2006) “Universal” and ethnic ideals of beautiful buttocks are best obtained by autologous micro fat grafting and liposuction. Clin Plast Surg 33:371–394CrossRefGoogle Scholar
  6. 6.
    Czerny V (1895) Plastischer Ersatz der Brustdruse durch ein Lipom. Zentralbl Chir 27:72Google Scholar
  7. 7.
    Coleman SR, Saboeiro AP (2007) Fat grafting to the breast revisited: safety and efficacy. Plast Reconstr Surg 119:775–785CrossRefGoogle Scholar
  8. 8.
    Rietjens M, De Lorenzi F, Rossetto F, Brenelli F, Manconi A, Martella S et al (2011) Safety of fat grafting in secondary breast reconstruction after cancer. J Plast Reconstr Aesthet Surg 64:477–483CrossRefGoogle Scholar
  9. 9.
    Petit JY, Botteri E, Lohsiriwat V, Rietjens M, De Lorenzi F, Garusi C, Rossetto F, Martella S, Manconi A, Bertolini F, Curigliano G, Veronesi P, Santillo B, Rotmensz N (2012) Locoregional recurrence risk after lipofilling in breast cancer patients. Ann Oncol 23:582–588CrossRefGoogle Scholar
  10. 10.
    Pereira LH, Sterodimas A (2008) Free fat transplantation for the aesthetic correction of mild pectus excavatum. Aesthetic Plast Surg 32:393–396CrossRefGoogle Scholar
  11. 11.
    Sterodimas A, Huanquipaco JC, de Souza Filho S, Bornia FA, Pitanguy I (2009) Autologous fat transplantation for the treatment of Parry–Romberg syndrome. J Plast Reconstr Aesthet Surg 62:e424–e426CrossRefGoogle Scholar
  12. 12.
    Gimble JM, Katz AJ, Bunnell BA (2007) Adipose-derived stem cells for regenerative medicine. Circ Res 100:1249–1260CrossRefGoogle Scholar
  13. 13.
    Faustini M, Bucco M, Chlapanidas T, Lucconi G, Marazzi M, Tosca MC, Gaetani P, Klinger M, Villani S, Ferretti VV, Vigo D, Torre ML (2010) Nonexpanded mesenchymal stem cells for regenerative medicine: yield in stromal vascular fraction from adipose tissues. Tissue Eng Part C Methods 16:1515–1521CrossRefGoogle Scholar
  14. 14.
    Bourin P, Peyrafitte JA, Fleury-Cappellesso S (2011) A first approach for the production of human adipose tissue-derived stromal cells for therapeutic use. Methods Mol Biol 702:331–343CrossRefGoogle Scholar
  15. 15.
    Guo J, Nguyen A, Banyard DA, Fadavi D, Toranto JD, Wirth GA, Paydar KZ, Evans GR, Widgerow AD (2016) Stromal vascular fraction: a regenerative reality? Part 2: mechanisms of regenerative action. J Plast Reconstr Aesthet Surg 69:180–188CrossRefGoogle Scholar
  16. 16.
    Masuda T, Furue M, Matsuda T (2004) Novel strategy for soft tissue augmentation based on transplantation of fragmented omentum and preadipocytes. Tissue Eng 10:1672–1683CrossRefGoogle Scholar
  17. 17.
    Zhu M, Zhou Z, Chen Y, Schreiber R, Ransom JT, Fraser JK, Hedrick MH, Pinkernell K, Kuo HC (2010) Supplementation of fat grafts with adipose-derived regenerative cells improves long-term graft retention. Ann Plast Surg 64:222–228CrossRefGoogle Scholar
  18. 18.
    Yoshimura K, Suga H, Eto H (2009) Adipose-derived stem/progenitor cells: roles in adipose tissue remodeling and potential use for soft tissue augmentation. Regen Med 4:265–273CrossRefGoogle Scholar
  19. 19.
    Schweizer R, Tsuji W, Gorantla VS, Marra KG, Rubin JP, Plock JA (2015) The role of adipose-derived stem cells in breast cancer progression and metastasis. Stem Cells Int 2015:120949CrossRefGoogle Scholar
  20. 20.
    Pu LL, Coleman SR, Cui X, Ferguson RE Jr, Vasconez HC (2008) Autologous fat grafts harvested and refined by the Coleman technique: a comparative study. Plast Reconstr Surg 122:932–937CrossRefGoogle Scholar
  21. 21.
    Delay E, Garson S, Tousson G, Sinna R (2009) Fat injection to the breast: technique, results, and indications based on 880 procedures over 10 years. Aesthet Surg J 29:360–376CrossRefGoogle Scholar
  22. 22.
    Phulpin B, Gangloff P, Tran N, Bravetti P, Merlin JL, Dolivet G (2009) Rehabilitation of irradiated head and neck tissues by autologous fat transplantation. Plast Reconstr Surg 123:1187–1197CrossRefGoogle Scholar
  23. 23.
    Baillargeon J, Rose DP (2006) Obesity, adipokines, and prostate cancer (review). Int J Oncol 28:737–745Google Scholar
  24. 24.
    Trayhurn P, Wood IS (2004) Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92:347–355CrossRefGoogle Scholar
  25. 25.
    Petit JY, Lohsiriwat V, Clough KB, Sarfati I, Ihrai T, Rietjens M, Veronesi P, Rossetto F, Scevola A, Delay E (2011) The oncologic outcome and immediate surgical complications of lipofilling in breast cancer patients: a multicenter study—Milan–Paris–Lyon experience of 646 lipofilling procedures. Plast Reconstr Surg 128:341–346CrossRefGoogle Scholar
  26. 26.
    Petit JY, Rietjens M, Botteri E, Rotmensz N, Bertolini F, Curigliano G, Rey P, Garusi C, De Lorenzi F, Martella S, Manconi A, Barbieri B, Veronesi P, Intra M, Brambullo T, Gottardi A, Sommario M, Lomeo G, Iera M, Giovinazzo V, Lohsiriwat V (2013) Evaluation of fat grafting safety in patients with intraepithelial neoplasia: a matched-cohort study. Ann Oncol 24:1479–1484CrossRefGoogle Scholar
  27. 27.
    Kronowitz SJ, Mandujano CC, Liu J, Kuerer HM, Smith B, Garvey P, Jagsi R, Hsu L, Hanson S, Valero V (2016) Lipo filling of the breast does not increase the risk of recurrence of breast cancer: a matched controlled study. Plast Reconstr Surg 137:385–393CrossRefGoogle Scholar
  28. 28.
    Gale KL, Rakha EA, Ball G, Tan VK, McCulley SJ, Macmillan RD (2015) A case-controlled study of the oncologic safety of fat grafting. Plast Reconstr Surg 135:1263–1275CrossRefGoogle Scholar
  29. 29.
    Petit JY, Maisonneuve P, Rotmensz N, Bertolini F, Rietjens M (2017) Fat grafting after invasive breast cancer: a matched case-control study. Plast Reconstr Surg 139:1292–1296CrossRefGoogle Scholar
  30. 30.
    Lu F, Li J, Gao J, Ogawa R, Ou C, Yang B (2009) Improvement of the survival of human autologous fat transplantation by using VEGF-transfected adipose-derived stem cells. Plast Reconstr Surg 124:1437–1446CrossRefGoogle Scholar
  31. 31.
    Yuksel E, Weinfeld AB, Cleek R, Wamsley S, Jensen J, Boutros S, Waugh JM, Shenaq SM, Spira M (2000) Increased free fat-graft survival with the long-term, local delivery of insulin, insulin-like growth factor-I, and basic fibroblast growth factor by PLGA/PEG microspheres. Plast Reconstr Surg 105:1712–1720CrossRefGoogle Scholar
  32. 32.
    Yoshimura K, Sato K, Aoi N, Kurita M, Hirohi T, Harii K (2008) Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells. Aesthet Plast Surg 32:48–55CrossRefGoogle Scholar
  33. 33.
    Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228CrossRefGoogle Scholar
  34. 34.
    Riordan NH, Ichim TE, Min WP, Wang H, Solano F, Lara F, Alfaro M, Rodriguez JP, Harman RJ, Patel AN, Murphy MP, Lee RR, Minev B (2009) Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis. J Transl Med 7:29CrossRefGoogle Scholar
  35. 35.
    Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP, Yoshimura K, Gimble JM (2013) Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy 15:641–648CrossRefGoogle Scholar
  36. 36.
    Kim YJ, Jeong JH (2014) Clinical application of adipose stem cells in plastic surgery. J Korean Med Sci 29:462–467CrossRefGoogle Scholar
  37. 37.
    Doi K, Tanaka S, Iida H, Eto H, Kato H, Aoi N, Kuno S, Hirohi T, Yoshimura K (2013) Stromal vascular fraction isolated from lipo-aspirates using an automated processing system: bench and bed analysis. J Tissue Eng Regen Med 7:864–870CrossRefGoogle Scholar
  38. 38.
    Aronowitz JA, Lockhart RA, Hakakian CS (2015) Mechanical versus enzymatic isolation of stromal vascular fraction cells from adipose tissue. Springerplus 4:713CrossRefGoogle Scholar
  39. 39.
    Matsumoto D, Sato K, Gonda K, Takaki Y, Shigeura T, Sato T, Aiba-Kojima E, Iizuka F, Inoue K, Suga H, Yoshimura K (2006) Cell-assisted lipotransfer: supportive use of human adipose-derived cells for soft tissue augmentation with lipoinjection. Tissue Eng 12:3375–3382CrossRefGoogle Scholar
  40. 40.
    Charles-de-Sá L, Gontijo-de-Amorim NF, Maeda Takiya C, Borojevic R, Benati D, Bernardi P, Sbarbati A, Rigotti G (2015) Antiaging treatment of the facial skin by fat graft and adipose-derived stem cells. Plast Reconstr Surg 135:999–1009CrossRefGoogle Scholar
  41. 41.
    Chatterjee S, Laliberte M, Blelloch S, Ratanshi I, Safneck J, Buchel E, Raouf A (2015) Adipose-derived stromal vascular fraction differentially expands breast progenitors in tissue adjacent to tumors compared to healthy breast tissue. Plast Reconstr Surg 136:414e–425eCrossRefGoogle Scholar
  42. 42.
    Mandel K, Yang Y, Schambach A, Glage S, Otte A, Hass R (2013) Mesenchymal stem cells directly interact with breast cancer cells and promote tumor cell growth in vitro and in vivo. Stem Cells Dev 22:3114–3127CrossRefGoogle Scholar
  43. 43.
    Rowan BG, Gimble JM, Sheng M, Anbalagan M, Jones RK, Frazier TP, Asher M, Lacayo EA, Friedlander PL, Kutner R, Chiu ES (2014) Human adipose tissue-derived stromal/stem cells promote migration and early metastasis of triple negative breast cancer xenografts. PLoS ONE 9:e89595CrossRefGoogle Scholar
  44. 44.
    Zimmerlin L, Donnenberg AD, Rubin JP, Basse P, Landreneau RJ, Donnenberg VS (2011) 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 17:93–106CrossRefGoogle Scholar
  45. 45.
    Iorns E, Drews-Elger K, Ward TM, Dean S, Clarke J, Berry D, El Ashry D, Lippman M (2012) A new mouse model for the study of human breast cancer metastasis. PLoS ONE 7:e47995CrossRefGoogle Scholar
  46. 46.
    Kølle SF, Fischer-Nielsen A, Mathiasen AB, Elberg JJ, Oliveri RS, Glovinski PV, Kastrup J, Kirchhoff M, Rasmussen BS, Talman ML, Thomsen C, Dickmeiss E, Drzewiecki KT (2013) Enrichment of autologous fat grafts with ex vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-controlled trial. Lancet 382:1113–1120CrossRefGoogle Scholar
  47. 47.
    Eto H, Ishimine H, Kinoshita K, Watanabe-Susaki K, Kato H, Doi K, Kuno S, Kurisaki A, Yoshimura K (2013) Characterization of human adipose tissue-resident hematopoietic cell populations reveals a novel macrophage subpopulation with CD34 expression and mesenchymal multipotency. Stem Cells Dev 22:985–997CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery 2019

Authors and Affiliations

  1. 1.Department of Plastic and Reconstructive Surgery, School of MedicineKyungpook National UniversityDaeguSouth Korea
  2. 2.V Plastic ClinicsDaeguSouth Korea
  3. 3.Department of Laboratory Animal Medicine, College of Veterinary MedicineKyungpook National UniversityDaeguSouth Korea
  4. 4.Department of Physiology, School of MedicineKyungpook National UniversityDaeguSouth Korea
  5. 5.Cell and Matrix Research Institute, School of MedicineKyungpook National UniversityDaeguSouth Korea
  6. 6.Department of Surgery, School of MedicineKyungpook National UniversityDaeguSouth Korea

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