Cell-supplemented autologous fat grafting: a review from bench to bedside

Abstract

Autologous fat grafting is routinely used in plastic and reconstructive surgery to improve contour deformities and appearance. However, retention of fat over time is inconsistent and unpredictable. Cell-assisted lipostransfer (CAL), the practice of using stem cell-containing portions of adipose to enrich fat grafts, has been found to be a promising area of research to increase not only the retention of volume but also increase collagen production, enhance angiogenesis, and direct the overall repair, remodeling, and regeneration of the recipient site. CAL, therefore, has a multitude of clinical applications, ranging from oncologic reconstruction following radiation to facial rejuvenation, among others. In this paper, we provide a comprehensive review of the current state of cell-supplemented fat transfer and discuss our understanding of cellular interactions in enriched fat grafts, techniques to improve the viability of fat, clinical translation of CAL, regulatory oversight, and future directions.

Keywords

Cell-assisted lipotransfer / adipose-derived stem cells / autologous fat grafting / regenerative medicine

References

[1] Neuber F. Fettransplantation. Available from: https://www.scirp.org/reference/referencespapers?referenceid=1812808 [Last accessed on 27 Sep 2024]

[2] Bellini E,Raposio E.The science behind autologous fat grafting.Ann Med Surg (Lond)2017;24:65-73 PMCID:PMC5694962

[3] Bircoll M.Cosmetic breast augmentation utilizing autologous fat and liposuction techniques.Plast Reconstr Surg1987;79:267-71

[4] Cortese A,Felicetta L.Free fat transplantation for facial tissue augmentation.J Oral Maxillofac Surg2000;58:164-9

[5] Coleman SR.Structural fat grafts: the ideal filler?.Clin Plast Surg2001;28:111-9.

[6] Simonacci F,Grieco MP,Raposio E.Procedure, applications, and outcomes of autologous fat grafting.Ann Med Surg (Lond)2017;20:49-60 PMCID:PMC5491488

[7] Sinno S,Brownstone N.Current thoughts on fat grafting: using the evidence to determine fact or fiction.Plast Reconstr Surg2016;137:818-24

[8] Boschert MT,Puckett CL.Analysis of lipocyte viability after liposuction.Plast Reconstr Surg2002;109:761-5

[9] Crawford JL,Colbert SH.Fine tuning lipoaspirate viability for fat grafting.Plast Reconstr Surg2010;126:1342-8

[10] Billings E Jr.Historical review and present status of free fat graft autotransplantation in plastic and reconstructive surgery.Plast Reconstr Surg1989;83:368-81

[11] Doi K,Eto H.Differential contributions of graft-derived and host-derived cells in tissue regeneration/remodeling after fat grafting.Plast Reconstr Surg2015;135:1607-17

[12] Kato H,Eto H.Degeneration, regeneration, and cicatrization after fat grafting: dynamic total tissue remodeling during the first 3 months.Plast Reconstr Surg2014;133:303e-13e

[13] Eto H,Matsumoto D.Characterization of structure and cellular components of aspirated and excised adipose tissue.Plast Reconstr Surg2009;124:1087-97

[14] Rodbell M.Metabolism of isolated fat cells: II. The similar effects of phospholipase C (clostridium perfringens alpha toxin) and of insulin on glucose and amino acid metabolism.J Biol Chem241:130-9.

[15] Bunnell BA,Gagliardi C,Ripoll C.Adipose-derived stem cells: isolation, expansion and differentiation.Methods2008;45:115-20 PMCID:PMC3668445

[16] Fu S,Xin M,Xiao R.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 Surg2013;132:363-73

[17] Zuk PA,Mizuno H.Multilineage cells from human adipose tissue: implications for cell-based therapies.Tissue Eng2001;7:211-28

[18] Strioga M,Darinskas A,Michalek J.Same or not the same?.Stem Cells Dev2012;21:2724-52

[19] Suga H,Aoi N.Adipose tissue remodeling under ischemia: death of adipocytes and activation of stem/progenitor cells.Plast Reconstr Surg2010;126:1911-23

[20] Hong KY,Kim HJ.The fate of the adipose-derived stromal cells during angiogenesis and adipogenesis after cell-assisted lipotransfer.Plast Reconstr Surg2018;141:365-75

[21] Puissant B,Bourin P.Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells.Br J Haematol2005;129:118-29

[22] Garza RM,Paik KJ.Studies in fat grafting: part IV. Adipose-derived stromal cell gene expression in cell-assisted lipotransfer.Plast Reconstr Surg2015;135:1045-55 PMCID:PMC4376612

[23] Suh A,Cress MJ.Adipose-derived cellular and cell-derived regenerative therapies in dermatology and aesthetic rejuvenation.Ageing Res Rev2019;54:100933

[24] Borrelli MR,Sokol J.Fat chance: the rejuvenation of irradiated skin.Plast Reconstr Surg Glob Open2019;7:e2092 PMCID:PMC6416118

[25] Coleman SR.Long-term survival of fat transplants: controlled demonstrations.Aesthetic Plast Surg1995;19:421-5

[26] Coleman SR.Facial recontouring with lipostructure.Clin Plast Surg1997;24:347-67.

[27] Tabit CJ,Fan K,Bradley JP.Fat grafting versus adipose-derived stem cell therapy: distinguishing indications, techniques, and outcomes.Aesthetic Plast Surg2012;36:704-13

[28] Harats M,Jaeger M.Adipocytes viability after suction-assisted lipoplasty: does the technique matter?.Aesthetic Plast Surg2016;40:578-83

[29] Hanson SE,Chang EI.A prospective, randomized comparison of clinical outcomes with different processing techniques in autologous fat grafting.Plast Reconstr Surg2022;150:955-62

[30] Keck M,Riedl O.Power assisted liposuction to obtain adipose-derived stem cells: impact on viability and differentiation to adipocytes in comparison to manual aspiration.J Plast Reconstr Aesthet Surg2014;67:e1-8

[31] Duscher D,Maan ZN.Ultrasound-assisted liposuction does not compromise the regenerative potential of adipose-derived stem cells.Stem Cells Transl Med2016;5:248-57 PMCID:PMC4729547

[32] Trivisonno A,Cannistra C.Harvest of superficial layers of fat with a microcannula and isolation of adipose tissue-derived stromal and vascular cells.Aesthet Surg J2014;34:601-13

[33] Alharbi Z,Almakadi S,Vogt M.Conventional vs. micro-fat harvesting: how fat harvesting technique affects tissue-engineering approaches using adipose tissue-derived stem/stromal cells.J Plast Reconstr Aesthet Surg2013;66:1271-8

[34] Chen YW,Liao X.Effect of suction pressures on cell yield and functionality of the adipose-derived stromal vascular fraction.J Plast Reconstr Aesthet Surg2017;70:257-66

[35] Sterodimas A,Nicaretta B,Papalambros E.Cell-assisted lipotransfer.Aesthet Surg J2010;30:78-81

[36] Aronowitz JA.Adipose stromal vascular fraction isolation: a head-to-head comparison of four commercial cell separation systems.Plast Reconstr Surg2013;132:932e-9e

[37] Chang H,Che JH.Safety of adipose-derived stem cells and collagenase in fat tissue preparation.Aesthetic Plast Surg2013;37:802-8

[38] Condé-Green A,Sherman LS.Shift toward mechanical isolation of adipose-derived stromal vascular fraction: review of upcoming techniques.Plast Reconstr Surg Glob Open2016;4:e1017 PMCID:PMC5055005

[39] Tiryaki T,Cohen SR,Kocak P.A 3-step mechanical digestion method to harvest adipose-derived stromal vascular fraction.Plast Reconstr Surg Glob Open2020;8:e2652 PMCID:PMC7159941

[40] Domenis R,Calabrese S.Adipose tissue derived stem cells: in vitro and in vivo analysis of a standard and three commercially available cell-assisted lipotransfer techniques.Stem Cell Res Ther2015;6:2 PMCID:PMC4417272

[41] Gentile P,Orlandi A.Breast reconstruction with enhanced stromal vascular fraction fat grafting: what is the best method?.Plast Reconstr Surg Glob Open2015;3:e406 PMCID:PMC4494476

[42] Gentile P,De Fazio D,Scioli MG.Mechanical and enzymatic digestion of autologous fat grafting (A-FG): fat volume maintenance and ad-svfs amount in comparison.Aesthetic Plast Surg2023;47:2051-62

[43] Di Taranto G,Visconti G.Qualitative and quantitative differences of adipose-derived stromal cells from superficial and deep subcutaneous lipoaspirates: a matter of fat.Cytotherapy2015;17:1076-89

[44] Faustini M,Chlapanidas T.Nonexpanded mesenchymal stem cells for regenerative medicine: yield in stromal vascular fraction from adipose tissues.Tissue Eng Part C Methods2010;16:1515-21

[45] Tsekouras A,Tsilimigras DI,Kontos M.Comparison of the viability and yield of adipose-derived stem cells (ASCs) from different donor areas.In Vivo2017;31:1229-34 PMCID:PMC5756658

[46] Grasys J,Pallua N.Content of soluble factors and characteristics of stromal vascular fraction cells in lipoaspirates from different subcutaneous adipose tissue depots.Aesthet Surg J2016;36:831-41

[47] Iyyanki T,Liu J,Beahm EK.Harvesting technique affects adipose-derived stem cell yield.Aesthet Surg J2015;35:467-76 PMCID:PMC4532626

[48] Matsumoto D,Gonda K.Cell-assisted lipotransfer: supportive use of human adipose-derived cells for soft tissue augmentation with lipoinjection.Tissue Eng2006;12:3375-82

[49] Yoshimura K,Aoi N.Progenitor-enriched adipose tissue transplantation as rescue for breast implant complications.Breast J2010;16:169-75

[50] Yoshimura K,Aoi N,Hirohi T.Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells.Aesthetic Plast Surg2008;32:48-55 PMCID:PMC2175019

[51] Kamakura T.Autologous cell-enriched fat grafting for breast augmentation.Aesthetic Plast Surg2011;35:1022-30

[52] Pérez-Cano R,Lasso JM.Prospective trial of adipose-derived regenerative cell (ADRC)-enriched fat grafting for partial mastectomy defects: the RESTORE-2 trial.Eur J Surg Oncol2012;38:382-9

[53] Li M.The efficacy of cell-assisted lipotransfer versus conventional lipotransfer in breast augmentation: a systematic review and meta-analysis.Aesthetic Plast Surg2021;45:1478-86

[54] Jeon HJ,Lee JH.A prospective study of the efficacy of cell-assisted lipotransfer with stromal vascular fraction to correct contour deformities of the autologous reconstructed breast.Aesthetic Plast Surg2021;45:853-63

[55] Kølle ST,Taudorf M.Ex vivo-expanded autologous adipose tissue-derived stromal cells ensure enhanced fat graft retention in breast augmentation: a randomized controlled clinical trial.Stem Cells Transl Med2020;9:1277-86 PMCID:PMC7581442

[56] Yoshimura K,Aoi N.Cell-assisted lipotransfer for facial lipoatrophy: efficacy of clinical use of adipose-derived stem cells.Dermatol Surg2008;34:1178-85

[57] Koh KS,Kim H.Clinical application of human adipose tissue-derived mesenchymal stem cells in progressive hemifacial atrophy (Parry-Romberg disease) with microfat grafting techniques using 3-dimensional computed tomography and 3-dimensional camera.Ann Plast Surg2012;69:331-7

[58] Gentile P,Pasin M.Adipose-derived stromal vascular fraction cells and platelet-rich plasma: basic and clinical evaluation for cell-based therapies in patients with scars on the face.J Craniofac Surg2014;25:267-72

[59] Chang Q,Dong Z,Lu F.Quantitative volumetric analysis of progressive hemifacial atrophy corrected using stromal vascular fraction-supplemented autologous fat grafts.Dermatol Surg2013;39:1465-73

[60] Sasaki GH.The safety and efficacy of cell-assisted fat grafting to traditional fat grafting in the anterior mid-face: an indirect assessment by 3D imaging.Aesthetic Plast Surg2015;39:833-46

[61] Tanikawa DYS,Bueno DF,Alonso N.Fat grafts supplemented with adipose-derived stromal cells in the rehabilitation of patients with craniofacial microsomia.Plast Reconstr Surg2013;132:141-52

[62] Gontijo-de-Amorim NF,Rigotti G.Mechanical supplementation with the stromal vascular fraction yields improved volume retention in facial lipotransfer: a 1-year comparative study.Aesthet Surg J2017;37:975-85

[63] Roshdy OH,Farid CI,Bayoumi NH.Stromal vascular fraction improves the durability of autologous fat temple augmentation - a split-face randomized study using ultrasound biomicroscopy.J Plast Reconstr Aesthet Surg2022;75:1870-7

[64] Gentile P.Lipofilling enriched with adipose-derived mesenchymal stem cells improves soft tissue deformities and reduces scar pigmentation: clinical and instrumental evaluation in plastic surgery.Aesthetic Plast Surg2023;47:2063-73

[65] Li H,Marra KG,Donnenberg AD.Adipogenic potential of adipose stem cell subpopulations.Plast Reconstr Surg2011;128:663-72 PMCID:PMC4167367

[66] Borrelli MR,Blackshear C.CD34+CD146+ adipose-derived stromal cells enhance engraftment of transplanted fat.Stem Cells Transl Med2020;9:1389-400 PMCID:PMC7581443

[67] Borrelli MR,Adem S.The antifibrotic adipose-derived stromal cell: grafted fat enriched with CD74+ adipose-derived stromal cells reduces chronic radiation-induced skin fibrosis.Stem Cells Transl Med2020;9:1401-13 PMCID:PMC7581454

[68] Bourin P,Casteilla L.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).Cytotherapy2013;15:641-8 PMCID:PMC3979435

[69] Zielins ER,Ransom RC.Enrichment of adipose-derived stromal cells for bmpr1a facilitates enhanced adipogenesis.Tissue Eng Part A2016;22:214-21 PMCID:PMC4779277

[70] Rigotti G,Galiè M.Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells.Plast Reconstr Surg2007;119:1409-22

[71] Luan A,Whittam AJ.Cell-assisted lipotransfer improves volume retention in irradiated recipient sites and rescues radiation-induced skin changes.Stem Cells2016;34:668-73 PMCID:PMC4868181

[72] Chiu CH.Does stromal vascular fraction ensure a higher survival in autologous fat grafting for breast augmentation?.Aesthet Surg J2019;39:41-52

[73] Wang L,Lu Y,Hu X.Is the resorption of grafted fat reduced in cell-assisted lipotransfer for breast augmentation?.Ann Plast Surg2015;75:128-34

[74] Peltoniemi HH,Miettinen S.Stem cell enrichment does not warrant a higher graft survival in lipofilling of the breast: a prospective comparative study.J Plast Reconstr Aesthet Surg2013;66:1494-503

[75] Laloze J,Gilhodes J.Cell-assisted lipotransfer: friend or foe in fat grafting?.J Tissue Eng Regen Med2018;12:e1237-50

[76] Report on autologous fat transplantation. ASPRS ad-hoc committee on new procedures, September 30, 1987.Plast Surg Nurs1987;7:140-1.

[77] Surgeons ASoP. Fat transfer/fat graft and fat injection: ASPS guiding principles. Available from: https://www.plasticsurgery.org/Documents/Health-Policy/Principles/principle-2015-post-mastectomy-fat-grafting.pdf [Last accessed on 28 Sep 2024]

[78] Tukiama R,Facina G,Zucca-Matthes G.Oncologic safety of autologous fat grafting after breast cancer surgical treatment: a matched cohort study.Plast Reconstr Surg2021;148:11-20

[79] Cohen O,Karp N.Determining the oncologic safety of autologous fat grafting as a reconstructive modality: an institutional review of breast cancer recurrence rates and surgical outcomes.Plast Reconstr Surg2017;140:382e-92e

[80] Hanson SE,Garvey PB.Oncologic safety and surveillance of autologous fat grafting following breast conservation therapy.Plast Reconstr Surg2020;146:215-25

[81] Mestak O,Fajfrova M,Mestak J.Evaluation of oncological safety of fat grafting after breast-conserving therapy: a prospective study.Ann Surg Oncol2016;23:776-81

[82] Goto H,Funakoshi Y.Adipose-derived stem cells enhance human breast cancer growth and cancer stem cell-like properties through adipsin.Oncogene2019;38:767-79

[83] Eterno V,Pavesi L.Adipose-derived Mesenchymal Stem Cells (ASCs) may favour breast cancer recurrence via HGF/c-Met signaling.Oncotarget2014;5:613-33 PMCID:PMC3996669

[84] Gehmert S,Prantl L,Alt E.Breast cancer cells attract the migration of adipose tissue-derived stem cells via the PDGF-BB/PDGFR-beta signaling pathway.Biochem Biophys Res Commun2010;398:601-5

[85] Kuhbier JW,Reimers K.Observed changes in the morphology and phenotype of breast cancer cells in direct co-culture with adipose-derived stem cells.Plast Reconstr Surg2014;134:414-23

[86] Rowan BG,Sheng M.Human adipose tissue-derived stromal/stem cells promote migration and early metastasis of triple negative breast cancer xenografts.PLoS One2014;9:e89595 PMCID:PMC3938488

[87] Orecchioni S,Martin-Padura I.Complementary populations of human adipose CD34+ progenitor cells promote growth, angiogenesis, and metastasis of breast cancer.Cancer Res2013;73:5880-91

[88] Charvet HJ,Wong MS.The oncologic safety of breast fat grafting and contradictions between basic science and clinical studies: a systematic review of the recent literature.Ann Plast Surg2015;75:471-9

[89] Calabrese C,Badylak S.Oncological safety of stromal vascular fraction enriched fat grafting in two-stage breast reconstruction after nipple sparing mastectomy: long-term results of a prospective study.Eur Rev Med Pharmacol Sci2018;22:4768-77

[90] Mazur S,Siennicka K,Chrapusta A.Safety of adipose-derived cell (stromal vascular fraction - SVF) augmentation for surgical breast reconstruction in cancer patients.Adv Clin Exp Med2018;27:1085-90

[91] Al Qurashi AA,Alzahrani IA.Efficacy of exclusive fat grafting for breast reconstruction: an updated systematic review and meta-analysis.Aesthetic Plast Surg2024;

[92] Administration USFaD. Federal court issues decision holding that US Stem Cell clinics and owner adulterated and misbranded stem cell products in violation of the law. Available from: https://www.fda.gov/news-events/press-announcements/federal-court-issues-decision-holding-us-stem-cell-clinics-and-owner-adulterated-and-misbranded-stem [Last accessed on 28 Sep 2024]

[93] Services USDoHaH. Regulatory considerations for human cells, tissues, and cellular andtissue-based products: minimal manipulation and homologous use. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/regulatory-considerations-human-cells-tissues-and-cellular-and-tissue-based-products-minimal [Last accessed on 28 Sep 2024]

[94] Raposio E.Clinical use of adipose-derived stem cells: European legislative issues.Ann Med Surg (Lond)2017;24:61-4 PMCID:PMC5709339

[95] Bae YC,Bae SH.Effects of human adipose-derived stem cells and stromal vascular fraction on cryopreserved fat transfer.Dermatol Surg2015;41:605-14

[96] Zanata F,Frazier T.Effect of cryopreservation on human adipose tissue and isolated stromal vascular fraction cells: in vitro and in vivo analyses.Plast Reconstr Surg2018;141:232e-43e

[97] Zheng W,Wang H.Effects of frozen stromal vascular fraction on the survival of cryopreserved fat tissue.Aesthetic Plast Surg2019;43:826-35 PMCID:PMC6522457