Skip to main content

Advertisement

Log in

Allogeneic Adipose-Derived Stem Cells Protect Fat Grafts at the Early Stage and Improve Long-Term Retention in Immunocompetent Rats

  • Original Article
  • Experimental/Special Topics
  • Published:
Aesthetic Plastic Surgery Aims and scope Submit manuscript

Abstract

Background

Syngeneic adipose-derived stem cells (ASCs) promote the survival of fat grafts. But it is unclear whether allogeneic ASCs have a similar protective effect. In this study, we investigated the protective effect of allogeneic ASCs in a fat graft model of immunocompetent rats.

Methods

Syngeneic and allogeneic ASCs were derived from Lewis (LEW) and Norway-Brown rats, respectively. Fifty-four LEW rats were divided into three groups. Each LEW rat was injected subcutaneously at two paravertebral spots with adipose granules premixed with DMEM (AFT group), syngeneic ASCs (SYNG group), or allogeneic ASCs (ALLG group). Fat grafts were harvested at 7 and 14 days to examine apoptosis rates and immunochemistry staining was performed for Perilipin A and CD34. At 3 months, fat graft volume retentions were measured. The proportion of regulatory T (Treg) cells and the ratio of CD4/CD8 cells in blood were analyzed at 7 days.

Results

Expression of Perilipin A and CD34 was higher in the ALLG group than the AFT group at 14 days (P < 0.05). The apoptosis rate in the ALLG group decreased in comparison with the AFT group at 7 and 14 days (P < 0.05). At 3 months, allogeneic ASCs increased fat graft volume retentions (P < 0.05). No difference was found in the proportion of Treg cells and CD4/CD8 cells ratio between groups. There were no statistically significant difference between ALLG and SYNG groups at all time points (P > 0.05).

Conclusions

Allogeneic ASCs protected fat grafts at the early stage and improved long-term volume retention in the fat graft model of immunocompetent rats with no or little obvious immune rejection.

No Level Assigned

This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Brayfield C, Marra K, Rubin JP (2010) Adipose stem cells for soft tissue regeneration. Handchir Mikrochir Plast Chir 42:124–128

    Article  CAS  PubMed  Google Scholar 

  2. Kassolis JD, Reynolds MA (2005) Evaluation of the adjunctive benefits of platelet-rich plasma in subantral sinus augmentation. J Craniofac Surg 16:280–287

    Article  PubMed  Google Scholar 

  3. Khouri RK, Eisenmann-Klein M, Cardoso E, Cooley BC, Kacher D, Gombos E, Baker TJ (2012) Brava and autologous fat transfer is a safe and effective breast augmentation alternative: results of a 6-year, 81-patient, prospective multicenter study. Plast Reconstr Surg 129:1173–1187

    Article  CAS  PubMed  Google Scholar 

  4. 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 12:3375–3382

    Article  CAS  PubMed  Google Scholar 

  5. Alt EU, Senst C, Murthy SN, Slakey DP, Dupin CL, Chaffin AE, Kadowitz PJ, Izadpanah R (2012) Aging alters tissue resident mesenchymal stem cell properties. Stem Cell Res 8:215–225

    Article  CAS  PubMed  Google Scholar 

  6. Choudhery MS, Badowski M, Muise A, Pierce J, Harris DT (2014) Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation. J Transl Med 12:8

    Article  PubMed Central  PubMed  Google Scholar 

  7. Cianfarani F, Toietta G, Di Rocco G, Cesareo E, Zambruno G, Odorisio T (2013) Diabetes impairs adipose tissue-derived stem cell function and efficiency in promoting wound healing. Wound Repair Regen 21:545–553

    Article  PubMed  Google Scholar 

  8. Kim HK, Kim YJ, Kim JT, Kwon CH, Kim YK, Bae YC, Kim DH, Jung JS (2008) Alterations in the proangiogenic functions of adipose tissue-derived stromal cells isolated from diabetic rats. Stem Cells Dev 17:669–680

    Article  CAS  PubMed  Google Scholar 

  9. Kubota Y, Kishi K, Satoh H, Tanaka T, Nakajima H, Nakajima T (2003) Transplanted endothelial progenitor cells augment the survival areas of rat dorsal flaps. Cell Transpl 12:647–657

    Article  Google Scholar 

  10. Piccinno MS, Veronesi E, Loschi P, Pignatti M, Murgia A, Grisendi G, Castelli I, Bernabei D, Candini O, Conte P, Paolucci P, Horwitz EM, De Santis G, Iughetti L, Dominici M (2013) Adipose stromal/stem cells assist fat transplantation reducing necrosis and increasing graft performance. Apoptosis 18:1274–1289

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Ayhan M, Senen D, Adanali G, Gorgu M, Erdogan B, Albayrak B (2001) Use of beta blockers for increasing survival of free fat grafts. Aesthet Plast Surg 25:338–342

    Article  CAS  Google Scholar 

  12. Yoshimura K, Asano Y, Aoi N, Kurita M, Oshima Y, Sato K, Inoue K, Suga H, Eto H, Kato H, Harii K (2010) Progenitor-enriched adipose tissue transplantation as rescue for breast implant complications. Breast J 16:169–175

    Article  PubMed  Google Scholar 

  13. Hamed S, Ben-Nun O, Egozi D, Keren A, Malyarova N, Kruchevsky D, Gilhar A, Ullmann Y (2012) Treating fat grafts with human endothelial progenitor cells promotes their vascularization and improves their survival in diabetes mellitus. Plast Reconstr Surg 130:801–811

    Article  CAS  PubMed  Google Scholar 

  14. Dulmovits BM, Herman IM (2012) Microvascular remodeling and wound healing: a role for pericytes. Int J Biochem Cell Biol 44:1800–1812

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Hong SJ, Traktuev DO, March KL (2010) Therapeutic potential of adipose-derived stem cells in vascular growth and tissue repair. Curr Opin Organ Transpl 15:86–91

    Article  Google Scholar 

  16. Gutierrez-Fernandez M, Rodriguez-Frutos B, Ramos-Cejudo J, Teresa Vallejo-Cremades M, Fuentes B, Cerdan S, Diez-Tejedor E (2013) Effects of intravenous administration of allogenic bone marrow- and adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke. Stem Cell Res Ther 4:11

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Haddad-Mashadrizeh A, Bahrami AR, Matin MM, Edalatmanesh MA, Zomorodipour A, Fallah A, Gardaneh M, Ahmadian Kia N, Sanjarmoosavi N (2013) Evidence for crossing the blood barrier of adult rat brain by human adipose-derived mesenchymal stromal cells during a 6-month period of post-transplantation. Cytotherapy 15:951–960

    Article  CAS  PubMed  Google Scholar 

  18. Paul A, Srivastava S, Chen G, Shum-Tim D, Prakash S (2013) Functional assessment of adipose stem cells for xenotransplantation using myocardial infarction immunocompetent models: comparison with bone marrow stem cells. Cell Biochem Biophys 67:263–273

    Article  CAS  PubMed  Google Scholar 

  19. Griffin MD, Ryan AE, Alagesan S, Lohan P, Treacy O, Ritter T (2013) Anti-donor immune responses elicited by allogeneic mesenchymal stem cells: what have we learned so far? Immunol Cell Biol 91:40–51

    Article  CAS  PubMed  Google Scholar 

  20. Seifert M, Stolk M, Polenz D, Volk HD (2012) Detrimental effects of rat mesenchymal stromal cell pre-treatment in a model of acute kidney rejection. Front Immunol 3:202

    Article  PubMed Central  PubMed  Google Scholar 

  21. Chung BH, Lim SW, Doh KC, Piao SG, Heo SB, Yang CW (2013) Human adipose tissue derived mesenchymal stem cells aggravate chronic cyclosporin nephrotoxicity by the induction of oxidative stress. PLoS One 8:e59693

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Zhao JH, Yi CG, Li L, Zheng Y, Wu KK, Liang LH, Xia W, Guo SZ (2012) Observations on the survival and neovascularization of fat grafts interchanged between C57BL/6-gfp and C57BL/6 mice. Plast Reconstr Surg 130:398E–406E

    Article  CAS  PubMed  Google Scholar 

  23. Li K, Gao J, Zhang Z, Li J, Cha P, Liao Y, Wang G, Lu F (2013) Selection of donor site for fat grafting and cell isolation. Aesthet Plast Surg 37:153–158

    Article  Google Scholar 

  24. Park DK, Ji YH, Dhong ES, Gu JH, Yoon ES (2012) Transplantation of rat adipose-derived stem cells (ASCs) to improve the survival of autologous aspirated fat grafts. Tissue Eng Regen Med 9:69–74

    Article  CAS  Google Scholar 

  25. Eto H, Kato H, Suga H, Aoi N, Doi K, Kuno S (2012) The fate of adipocytes after nonvascularized fat grafting: evidence of early death and replacement of adipocytes. Plast Reconstr Surg 129:1081–1092

    Article  CAS  PubMed  Google Scholar 

  26. Zhu M, Zhou ZY, 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 64:222–228

    Article  CAS  PubMed  Google Scholar 

  27. Bauer-Kreisel P, Goepferich A, Blunk T (2010) Cell-delivery therapeutics for adipose tissue regeneration. Adv Drug Deliv Rev 62:798–813

    Article  CAS  PubMed  Google Scholar 

  28. Kilroy GE, Foster SJ, Wu X, Ruiz J, Sherwood S, Heifetz A, Ludlow JW, Stricker DM, Potiny S, Green P, Halvorsen YD, Cheatham B, Storms RW, Gimble JM (2007) Cytokine profile of human adipose-derived stem cells: expression of angiogenic, hematopoietic, and pro-inflammatory factors. J Cell Physiol 212:702–709

    Article  CAS  PubMed  Google Scholar 

  29. Fu S, Luan J, Xin M, Wang Q, Xiao R, Gao Y (2013) Fate of adipose-derived stromal vascular fraction cells after co-implantation with fat grafts: evidence of cell survival and differentiation in ischemic adipose tissue. Plast Reconstr Surg 132:363–373

    Article  CAS  PubMed  Google Scholar 

  30. Kakudo N, Tanaka Y, Morimoto N, Ogawa T, Kushida S, Hara T, Kusumoto K (2013) Adipose-derived regenerative cell (ADRC)-enriched fat grafting: optimal cell concentration and effects on grafted fat characteristics. J Transl Med 11:254

    Article  PubMed Central  PubMed  Google Scholar 

  31. Schu S, Nosov M, O’Flynn L, Shaw G, Treacy O, Barry F, Murphy M, O’Brien T, Ritter T (2012) Immunogenicity of allogeneic mesenchymal stem cells. J Cell Mol Med 16:2094–2103

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Huang XP, Sun Z, Miyagi Y, McDonald Kinkaid H, Zhang L, Weisel RD, Li RK (2010) Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long-term benefits for myocardial repair. Circulation 122:2419–2429

    Article  CAS  PubMed  Google Scholar 

  33. Gu HJ, Xiong ZY, Yin XF, Li B, Mei N, Li GZ, Wang C (2014) Bone regeneration in a rabbit ulna defect model: use of allogeneic adipose-derived stem cells with low immunogenicity. Cell Tissue Res 358:453–464

    Article  CAS  PubMed  Google Scholar 

  34. Chidgey AP, Seach N, Dudakov J, Hammett MV, Boyd RL (2008) Strategies for reconstituting and boosting T cell-based immunity following haematopoietic stem cell transplantation: pre-clinical and clinical approaches. Semin Immunol 30:457–477

    Article  Google Scholar 

Download references

Acknowledgments

We express our gratitude to Dr. Zhang Kui and Dr. Zhang Wenbin for their expert suggestions regarding the manuscript. This work was financially supported by the National Nature Science Foundation of China (81372078) (81301632).

Conflict of interest

None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Dahai Hu or Xiaoyan Liu.

Additional information

Jun Zhang and Yunchuan Wang have contributed equally to this work and agreed to share the first authorship position together. Xiaoyan Liu is the primary corresponding author of this article and Dahai Hu is the co-corresponding author.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Online Resource 1

The proportion of peripheral blood CD4/CD25/Foxp3 Treg cells. At 7 days, an average proportion of Treg in the AFT, SYNG, and ALLG groups were 6.6 ± 1.3, 7.3 ± 1.4 and 7.2 ± 1.0 % respectively (n = 6). Treg cells regulatory T cells

Online Resource 2

Viable adipocytes were measured by Perilipin A staining in fat grafts. Perilipin A-positive adipocytes with normal size were viable adipocytes,as indicated by the blue arrows, while the dead adipocytes were Perilipin A-negative even with normal size,as indicated by the white arrows. Scale bar 200 μm

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, J., Wang, Y., Zhao, B. et al. Allogeneic Adipose-Derived Stem Cells Protect Fat Grafts at the Early Stage and Improve Long-Term Retention in Immunocompetent Rats. Aesth Plast Surg 39, 625–634 (2015). https://doi.org/10.1007/s00266-015-0505-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00266-015-0505-9

Keywords

Navigation