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Allogeneic adipose-derived stem cells promote survival of fat grafts in immunocompetent diabetic rats

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Abstract

Autologous adipose-derived stem cells (ADSCs) can protect fat grafts in cell-assisted lipotransfer (CAL). However, diabetes alters the intrinsic properties of ADSCs and impairs their function so that they lack these protective effects. We investigate whether allogeneic ADSCs from healthy donors could protect fat grafts in immunocompetent diabetic rats. Syngeniec adipose tissues and ADSCs were derived from diabetic Lewis (LEW) rats, whereas allogeneic ADSCs were from healthy brown-Norway rats. A grafted mixture containing 0.7 ml granule fat and 0.3 ml 6 × 106 allogeneic/syngeneic ADSCs was injected subcutaneously on the skulls of diabetic LEW rats. Fat samples were harvested to evaluate the levels of injury and vascularization as shown by perilipin A, CD34 and VEGF at 14 days. The immune response was evaluated with a lymphocytotoxicity test and the CD4/CD8 ratio in peripheral blood at 14 days. The volume retention of fat grafts was measured at 3 months. Healthy allogeneic ADSCs increased the expression levels of perilipin A, CD34 and VEGF at 14 days. The volume retention of fat grafts was improved by allogeneic ADSCs at 3 months. ADSCs were demonstrated to have low immunogenicity by the lymphocyte proliferation test and immunophenotype including MHC and co-stimulatory markers. The lymphocytotoxicity test and CD4/CD8 ratio indicated no obvious immune response elicited by allogeneic ADSCs. Thus, healthy allogeneic ADSCs can promote the survival of fat grafts in this immunocompetent diabetic rat model, with little or no obvious immune rejection.

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References

  • 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 

  • Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30:42–48

    Article  PubMed  Google Scholar 

  • Butala P, Hazen A, Szpalski C, Sultan SM, Coleman SR, Warren SM (2012) Endogenous stem cell therapy enhances fat graft survival. Plast Reconstr Surg 130:293–306

    Article  CAS  PubMed  Google Scholar 

  • Cheng HY, Ghetu N, Huang WC, Wang YL, Wallace CG, Wen CJ, Chen HC, Shih LY, Lin CF, Hwang SM, Liao SK, Wei FC (2014) Syngeneic adipose-derived stem cells with short-term immunosuppression induce vascularized composite allotransplantation tolerance in rats. Cytotherapy 16:369–380

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • Choi YD, Shin HS, Mok JO (2014) Impaired survival of autologous fat grafts by diabetes mellitus in an animal model: a pilot study. Aesthet Surg J 34:168–174

    Article  PubMed  Google Scholar 

  • 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 

  • English K, Mahon BP (2011) Allogeneic mesenchymal stem cells: agents of immune modulation. J Cell Biochem 112:1963–1968

    Article  CAS  PubMed  Google Scholar 

  • Eto H, Kato H, Suga H, Aoi N, Doi K, Kuno S, Yoshimura K (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 

  • Fadini GP, Agostini C, Avogaro A (2005a) Endothelial progenitor cells and vascular biology in diabetes mellitus: current knowledge and future perspectives. Curr Diabetes Rev 1:41–58

    Article  CAS  PubMed  Google Scholar 

  • Fadini GP, Miorin M, Facco M, Bonamico S, Baesso I, Grego F, Menegolo M, Kreutzenberg SV de, Tiengo A, Agostini C, Avogaro A (2005b) Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol 45:1449–1457

  • Fu S, Luan J, Xin MQ, Wang Q, Xiao R, Gao YZ (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 

  • Giordano A, Galderisi U, Marino IR (2007) From the laboratory bench to the patient's bedside: an update on clinical trials with mesenchymal stem cells. J Cell Physiol 211:27–35

    Article  CAS  PubMed  Google Scholar 

  • Gu HJ, Xiong ZY, Yin XF, Li B, Mei N, Li GZ, Wang C (2014a) 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 

  • Gu LH, Zhang TT, Li Y, Yan HJ, Qi H, Li FR (2014b) Immunogenicity of allogeneic mesenchymal stem cells transplanted via different routes in diabetic rats. Cell Mol Immunol 12:444–455

    Article  PubMed  PubMed Central  Google Scholar 

  • 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  PubMed Central  Google Scholar 

  • Haddad R, Saldanha-Araujo F (2014) Mechanisms of T-cell immunosuppression by mesenchymal stromal cells: what do we know so far? Biomed Res Int 2014:216806

    PubMed  PubMed Central  Google Scholar 

  • 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 

  • 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 

  • He XS, Zhong XC, Ni YD, Liu ML, Liu SH, Lan XL (2013) Effect of ASCs on the graft survival rates of fat particles in rabbits. J Plast Surg Hand Su 47:3–7

    Article  Google Scholar 

  • 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 

  • Illouz YG, Sterodimas A (2009) Autologous fat transplantation to the breast: a personal technique with 25 years of experience. Aesthet Plast Surg 33:706–715

    Article  Google Scholar 

  • Isakova IA, Lanclos C, Bruhn J, Kuroda MJ, Baker KC, Krishnappa V, Phinney DG (2014) Allo-reactivity of mesenchymal stem cells in rhesus macaques is dose and haplotype dependent and limits durable cell engraftment in vivo. PLoS One 9:e87238

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiang X, Liu C, Hao J, Guo D, Guo J, Yao J, Jiang K, Cui Z, Zhu L, Sun W, Lin L, Liang J (2014) CD4(+)CD25(+) regulatory T cells are not required for mesenchymal stem cell function in fully MHC-mismatched mouse cardiac transplantation. Cell Tissue Res 358:503–514

    Article  CAS  PubMed  Google Scholar 

  • Kang SH, Chung YG, Oh IH, Kim YS, Min KO, Chung JY (2014) Bone regeneration potential of allogeneic or autogeneic mesenchymal stem cells loaded onto cancellous bone granules in a rabbit radial defect model. Cell Tissue Res 355:81–88

    Article  CAS  PubMed  Google Scholar 

  • Karagianni M, Kraneburg U, Kluter H, Machens HG, Bieback K, Schantz JT, Papadopulos N (2013) Autologous fat grafts and supportive enrichment with adipose tissue stromal cells. Handchir Mikrochir Plast Chir 45:93–98

    Article  CAS  PubMed  Google Scholar 

  • Kazemi-Darabadi S, Sarrafzadeh-Rezaei F, Farshid AA, Dalir-Naghadeh B (2014) Allogenous skin fibroblast transplantation enhances excisional wound healing following alloxan diabetes in sheep, a randomized controlled trial. Int J Surg 12:751–756

    Article  PubMed  Google Scholar 

  • 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 

  • 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 

  • Kim I, Bang SI, Lee SK, Park SY, Kim M, Ha H (2014) Clinical implication of allogenic implantation of adipogenic differentiated adipose-derived stem cells. Stem Cells Transl Med 3:1312–1321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 Transplant 12:647–657

    Article  PubMed  Google Scholar 

  • Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringden O (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371:1579–1586

    Article  PubMed  Google Scholar 

  • Li CD, Zhang WY, Jiang XX, Mao N (2007) Human-placenta-derived mesenchymal stem cells inhibit proliferation and function of allogeneic immune cells. Cell Tissue Res 330:437–446

    Article  PubMed  Google Scholar 

  • Li KC, Gao JH, Zhang ZD, Li J, Cha PF, Liao YJ, Wang G, Lu F (2013) Selection of donor site for fat grafting and cell isolation. Aesthet Plast Surg 37:153–158

    Article  Google Scholar 

  • Lin C-S, Lin G, Lue TF (2012) Allogeneic and xenogeneic transplantation of adipose-derived stem cells in immunocompetent recipients without immunosuppressants. Stem Cells Dev 21:2770–2778

    Article  PubMed  PubMed Central  Google Scholar 

  • Lohan P, Coleman CM, Murphy JM, Griffin MD, Ritter T, Ryan AE (2014) Changes in immunological profile of allogeneic mesenchymal stem cells after differentiation: should we be concerned? Stem Cell Res Ther 5:99

    Article  PubMed  PubMed Central  Google Scholar 

  • Mannon PJ (2011) Remestemcel-L: human mesenchymal stem cells as an emerging therapy for Crohn's disease. Expert Opin Biol Ther 11:1249–1256

    Article  PubMed  Google Scholar 

  • Mukonoweshuro B, Brown CJ, Fisher J, Ingham E (2014) Immunogenicity of undifferentiated and differentiated allogeneic mouse mesenchymal stem cells. J Tissue Eng 5:2041731414534255

    Article  PubMed  PubMed Central  Google Scholar 

  • Park B, Kong JS, Kang S, Kim YW (2011) The effect of epidermal growth factor on autogenous fat graft. Aesthet Plast Surg 35:738–744

    Article  Google Scholar 

  • 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 

  • Peeters WJ, Nanhekhan L, Van Ongeval C, Fabre G, Vandevoort M (2009) Fat necrosis in deep inferior epigastric perforator flaps: an ultrasound-based review of 202 cases. Plast Reconstr Surg 124:1754–1758

    Article  CAS  PubMed  Google Scholar 

  • Philips BJ, Grahovac TL, Valentin JE, Chung CW, Bliley JM, Pfeifer ME, Roy SB, Dreifuss S, Kelmendi-Doko A, Kling RE, Ravuri SK, Marra KG, Donnenberg VS, Donnenberg AD, Rubin JP (2013) Prevalence of endogenous CD34(+) adipose stem cells predicts human fat graft retention in a xenograft model. Plast Reconstr Surg 132:845–858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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  PubMed Central  Google Scholar 

  • Poncelet AJ, Vercruysse J, Saliez A, Gianello P (2007) Although pig allogeneic mesenchymal stem cells are not immunogenic in vitro, intracardiac injection elicits an immune response in vivo. Transplantation 83:783–790

    Article  PubMed  Google Scholar 

  • Requena L (2007) Normal subcutaneous fat, necrosis of adipocytes and classification of the panniculitides. Semin Cutan Med Surg 26:66–70

    Article  CAS  PubMed  Google Scholar 

  • 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  PubMed Central  Google Scholar 

  • Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, Moretta L (2006) Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation. Blood 107:1484–1490

    Article  CAS  PubMed  Google Scholar 

  • Tabit CJ, Slack GC, Fan K, Wan DC, Bradley JP (2012) Fat grafting versus adipose-derived stem cell therapy: distinguishing indications, techniques, and outcomes. Aesthet Plast Surg 36:704–713

    Article  Google Scholar 

  • Trojahn Kølle SF, Oliveri RS, Glovinski PV, Elberg JJ, Fischer-Nielsen A, Drzewiecki KT (2012) Importance of mesenchymal stem cells in autologous fat grafting: a systematic review of existing studies. J Plast Surg Hand Surg 46:59–68

    Article  PubMed  Google Scholar 

  • Yang M, Zhang F, Sailes FC, Zhang EW, Lin SY, Das SK (2012) Role of anti-TNF-alpha therapy in fat graft preservation. Ann Plast Surg 68:531–535

    Article  CAS  PubMed  Google Scholar 

  • Yoshimura K, Satob K (2007) Clinical experiences of cell-assisted lipotransfer for soft tissue augmentation. Stem Cells 25:3278

    Google Scholar 

  • 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 4:265–273

    Article  PubMed  Google Scholar 

  • Zhang J, Wang Y, Zhao B, Fan L, Bai X, Yang L, Chang P, Hu D, Liu X (2015) Allogeneic adipose-derived stem cells protect fat grafts at the early stage and improve long-term retention in immunocompetent rats. Aesthet Plast Surg 39:625–634

    Article  Google Scholar 

  • 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 

  • Zhao JH, Yi CG, Zheng Y, Li L, Qiu X, Xia W, Su YJ, Diao JS, Guo SZ (2013) Enhancement of fat graft survival by bone marrow-derived mesenchymal stem cell therapy. Plast Reconstr Surg 132:1149–1157

    Article  CAS  PubMed  Google Scholar 

  • Zhu X, Shi W, Tai W, Liu F (2012) The comparition of biological characteristics and multilineage differentiation of bone marrow and adipose derived mesenchymal stem cells. Cell Tissue Res 350:277–287

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Graduate School, Second Military Medical University, Shanghai, 200433, People’s Republic of China

    Jun Zhang & Xiaoyan Liu

  2. Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China

    Xiaozhi Bai, Bin Zhao, Yunchuan Wang, Linlin Su, Xujie Wang, Shichao Han, Jianxin Gao, Xiaolong Hu & Dahai Hu

  3. Department of Plastic Surgery, General Hospital of Shenyang Military Area Command of PLA, 83 Wenhua Road, Shenyang, Liaoning, 110016, People’s Republic of China

    Peng Chang & Xiaoyan Liu

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  1. Jun Zhang
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  2. Xiaozhi Bai
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  3. Bin Zhao
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  4. Yunchuan Wang
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  5. Linlin Su
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  6. Peng Chang
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  7. Xujie Wang
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  8. Shichao Han
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  9. Jianxin Gao
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  10. Xiaolong Hu
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  11. Dahai Hu
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  12. Xiaoyan Liu
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Correspondence to Xiaoyan Liu.

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Jun Zhang, Xiaozhi Bai and Bin Zhao contributed equally to this work and should be considered as equal first authors.

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Zhang, J., Bai, X., Zhao, B. et al. Allogeneic adipose-derived stem cells promote survival of fat grafts in immunocompetent diabetic rats. Cell Tissue Res 364, 357–367 (2016). https://doi.org/10.1007/s00441-015-2334-1

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