Autologous Fat Grafting—A Panacea for Scar Tissue Therapy?
Abstract
:1. Introduction
2. Autologous Fat Grafting as a New Approach to Scar Treatment with Regenerative Potential
Properties of Adipose-Derived Stem Cells and Their Potential Effects on Scars
3. Techniques and Clinical Implication of Autologous Fat Grafting
3.1. Effects of Autologous Fat Grafting on Scar
3.2. Scar Appearance and Skin Characteristics
3.3. Volume and Scar Contour
3.4. Fibrosis and Functional Impairment
3.5. Autologous Far Grafting and Pain Reduction
4. Clinical Applications
5. Limitations of Current Studies and Future Directions
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Li, L.; Pan, S.; Ni, B.; Lin, Y. Improvement in autologous human fat transplant survival with SVF plus VEGF–PLA nano-sustained release microspheres. Cell Biol. Int. 2014, 38, 962–970. [Google Scholar] [CrossRef]
- 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. Surg. 2023, 47, 2063–2073. [Google Scholar] [CrossRef] [PubMed]
- Jatin, B.; Karki, D.; Ahluwalia, C.; Muthukumar, V.; Karki, D. Lipofilling—A Regenerative Alternate for Remodeling Burn Scars: A Clinico-Immunohistopathological Study. Indian J. Plast. Surg. 2023, 56, 357–366. [Google Scholar] [CrossRef]
- Brayfield, C.C.; Marra, K.; Rubin, J.P. Adipose Stem Cells for Soft Tissue Regeneration. Handchir. Mikrochir. Plast. Chir. 2010, 42, 124–128. [Google Scholar] [CrossRef] [PubMed]
- Hanson, S.E. The Future of Fat Grafting. Aesthetic Surg. J. 2021, 41 (Suppl. S1), S69–S74. [Google Scholar] [CrossRef] [PubMed]
- Riyat, H.; Touil, L.L.; Briggs, M.; Shokrollahi, K. Autologous fat grafting for scars, healing and pain: A review. Scars Burn. Health 2017, 3, 205951311772820. [Google Scholar] [CrossRef]
- Zocchi, M.L.; Prantl, L.; Oliinyk, D.; Knoedler, L.; Siegmund, A.; Ahmad, N.; Duscher, D.; Larcher, L.; Raposio, E.; Pagani, A. Potential benefits of adipose–derived SVF and MSCs to regenerate damaged tissues from alloplastic synthetic materials. Eur. J. Plast. Surg. 2024, 47, 48. [Google Scholar] [CrossRef]
- Spiekman, M.; Van Dongen, J.A.; Willemsen, J.C.; Hoppe, D.L.; Van Der Lei, B.; Harmsen, M.C. The power of fat and its adipose-derived stromal cells: Emerging concepts for fibrotic scar treatment: Adipose tissue and ADSC for fibrotic scar treatment. J. Tissue Eng. Regen. Med. 2017, 11, 3220–3235. [Google Scholar] [CrossRef]
- Stachura, A.; Paskal, W.; Pawlik, W.; Mazurek, M.J.; Jaworowski, J. The Use of Adipose-Derived Stem Cells (ADSCs) and Stromal Vascular Fraction (SVF) in Skin Scar Treatment—A Systematic Review of Clinical Studies. JCM 2021, 10, 3637. [Google Scholar] [CrossRef]
- Rigotti, G.; Charles-de-Sá, L.; Gontijo-de-Amorim, N.F.; Takiya, C.M.; Amable, P.R.; Borojevic, R.; Benati, D.; Bernardi, P.; Sbarbati, A. Expanded Stem Cells, Stromal-Vascular Fraction, and Platelet-Rich Plasma Enriched Fat: Comparing Results of Different Facial Rejuvenation Approaches in a Clinical Trial. Aesthet. Surg. J. 2016, 36, 261–270. [Google Scholar] [CrossRef]
- De Ugarte, D.A.; Morizono, K.; Elbarbary, A.; Alfonso, Z.; Zuk, P.A.; Zhu, M.; Dragoo, J.L.; Ashjian, P.; Thomas, B.; Benhaim, P.; et al. Comparison of Multi-Lineage Cells from Human Adipose Tissue and Bone Marrow. Cells Tissues Organs 2003, 174, 101–109. [Google Scholar] [CrossRef]
- Rydén, M.; Dicker, A.; Götherström, C.; Åström, G.; Tammik, C.; Arner, P.; Le Blanc, K. Functional characterization of human mesenchymal stem cell-derived adipocytes. Biochem. Biophys. Res. Commun. 2003, 311, 391–397. [Google Scholar] [CrossRef] [PubMed]
- Gimble, J.M.; Guilak, F. Adipose-derived adult stem cells: Isolation, characterization, and differentiation potential. Cytotherapy 2003, 5, 362–369. [Google Scholar] [CrossRef]
- Rehman, J.; Traktuev, D.; Li, J.; Merfeld-Clauss, S.; Temm-Grove, C.J.; Bovenkerk, J.E.; Pell, C.L.; Johnstone, B.H.; Considine, R.V.; March, K.L. Secretion of Angiogenic and Antiapoptotic Factors by Human Adipose Stromal Cells. Circulation 2004, 109, 1292–1298. [Google Scholar] [CrossRef]
- Cao, Y.; Sun, Z.; Liao, L.; Meng, Y.; Han, Q.; Zhao, R.C. Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo. Biochem. Biophys. Res. Commun. 2005, 332, 370–379. [Google Scholar] [CrossRef]
- Tsuji, W. Adipose-derived stem cells: Implications in tissue regeneration. WJSC 2014, 6, 312. [Google Scholar] [CrossRef]
- Chen, X.; Yan, L.; Guo, Z.; Chen, Z.; Chen, Y.; Li, M.; Huang, C.; Zhang, X.; Chen, L. Adipose-derived mesenchymal stem cells promote the survival of fat grafts via crosstalk between the Nrf2 and TLR4 pathways. Cell Death Dis. 2016, 7, e2369. [Google Scholar] [CrossRef] [PubMed]
- Liu, T.; Zhang, L.; Joo, D.; Sun, S.C. NF-κB signaling in inflammation. Signal Transduct. Target. Ther. 2017, 2, 17023. [Google Scholar] [CrossRef]
- Ting, H.K.; Chen, C.L.; Meng, E.; Cherng, J.-H.; Chang, S.-J.; Kao, C.-C.; Yang, M.-H.; Leung, F.-S.; Wu, S.-T. Inflammatory Regulation by TNF-α-Activated Adipose-Derived Stem Cells in the Human Bladder Cancer Microenvironment. Int. J. Mol. Sci. 2021, 22, 3987. [Google Scholar] [CrossRef] [PubMed]
- Yu, H.; Pardoll, D.; Jove, R. STATs in cancer inflammation and immunity: A leading role for STAT3. Nat. Rev. Cancer 2009, 9, 798–809. [Google Scholar] [CrossRef]
- Hutchins, A.P.; Poulain, S.; Miranda-Saavedra, D. Genome-wide analysis of STAT3 binding in vivo predicts effectors of the anti-inflammatory response in macrophages. Blood 2012, 119, e110–e119. [Google Scholar] [CrossRef]
- Wang, Y.; Chu, Y.; Yue, B.; Ma, X.; Zhang, G.; Xiang, H.; Liu, Y.; Wang, T.; Wu, X.; Chen, B. Adipose-derived mesenchymal stem cells promote osteosarcoma proliferation and metastasis by activating the STAT3 pathway. Oncotarget 2017, 8, 23803–23816. [Google Scholar] [CrossRef]
- Xia, T.; Zhang, M.; Lei, W.; Yang, R.; Fu, S.; Fan, Z.; Yang, Y.; Zhang, T. Advances in the role of STAT3 in macrophage polarization. Front. Immunol. 2023, 14, 1160719. [Google Scholar] [CrossRef]
- Hutchins, A.P.; Diez, D.; Miranda-Saavedra, D. The IL-10/STAT3-mediated anti-inflammatory response: Recent developments and future challenges. Brief. Funct. Genom. 2013, 12, 489–498. [Google Scholar] [CrossRef] [PubMed]
- Rigotti, G.; Marchi, A.; Galiè, M.; Baroni, G.; Benati, D.; Krampera, M.; Pasini, A.; Sbarbati, A. Clinical Treatment of Radiotherapy Tissue Damage by Lipoaspirate Transplant: A Healing Process Mediated by Adipose-Derived Adult Stem Cells. Plast. Reconstr. Surg. 2007, 119, 1409–1422. [Google Scholar] [CrossRef] [PubMed]
- Garza, R.M.; Paik, K.J.A.; Chung, M.T.B.; Duscher, D.; Gurtner, G.C.; Longaker, M.T.M.; Wan, D.C. Studies in Fat Grafting: Part, I.I.I. Fat Grafting Irradiated Tissue—Improved Skin Quality and Decreased Fat Graft Retention. Plast. Reconstr. Surg. 2014, 134, 249–257. [Google Scholar] [CrossRef]
- Sultan, S.M.; Stern, C.S.; Allen, R.J.; Thanik, V.D.; Chang, C.C.; Nguyen, P.D.; Canizares, O.; Szpalski, C.; Saadeh, P.B.; Warren, S.M.; et al. Human Fat Grafting Alleviates Radiation Skin Damage in a Murine Model. Plast. Reconstr. Surg. 2011, 128, 363–372. [Google Scholar] [CrossRef]
- Han, T.T.Y.; Toutounji, S.; Amsden, B.G.; Flynn, L.E. Adipose-derived stromal cells mediate in vivo adipogenesis, angiogenesis and inflammation in decellularized adipose tissue bioscaffolds. Biomaterials 2015, 72, 125–137. [Google Scholar] [CrossRef]
- Shibuya, M. Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes Cancer 2011, 2, 1097–1105. [Google Scholar] [CrossRef]
- Murakami, M.; Simons, M. Fibroblast growth factor regulation of neovascularization. Curr. Opin. Hematol. 2008, 15, 215–220. [Google Scholar] [CrossRef] [PubMed]
- Wang, Q.; Zhou, M.; Zhang, H.; Hou, Z.; Liu, D. Hypoxia Treatment of Adipose Mesenchymal Stem Cells Promotes the Growth of Dermal Papilla Cells via HIF-1α and ERK1/2 Signaling Pathways. Int. J. Mol. Sci. 2023, 24, 11198. [Google Scholar] [CrossRef] [PubMed]
- Takuwa, Y. Roles of sphingosine-1-phosphate signaling in angiogenesis. WJBC 2010, 1, 298. [Google Scholar] [CrossRef]
- Yuan, K.; Jin, Y.; Lin, M.T. Expression of Tie-2, angiopoietin-1, angiopoietin-2, ephrinB2 and EphB4 in pyogenic granuloma of human gingiva implicates their roles in inflammatory angiogenesis. J. Periodontal Res. 2000, 35, 165–171. [Google Scholar] [CrossRef]
- Groppa, E.; Brkic, S.; Uccelli, A.; Wirth, G.; Korpisalo-Pirinen, P.; Filippova, M.; Dasen, B.; Sacchi, V.; Muraro, M.G.; Trani, M.; et al. EphrinB2/EphB4 signaling regulates non-sprouting angiogenesis by VEGF. EMBO Rep. 2018, 19, e45054. [Google Scholar] [CrossRef]
- Farooq, M.; Khan, A.W.; Kim, M.S.; Choi, S. The Role of Fibroblast Growth Factor (FGF) Signaling in Tissue Repair and Regeneration. Cells 2021, 10, 3242. [Google Scholar] [CrossRef]
- Mazini, L.; Rochette, L.; Admou, B.; Amal, S.; Malka, G. Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing. Int. J. Mol. Sci. 2020, 21, 1306. [Google Scholar] [CrossRef]
- Hu, Y.; Xiong, Y.; Zhu, Y.; Zhou, F.; Liu, X.; Chen, S.; Li, Z.; Qi, S.; Chen, L. Copper-Epigallocatechin Gallate Enhances Therapeutic Effects of 3D-Printed Dermal Scaffolds in Mitigating Diabetic Wound Scarring. ACS Appl. Mater. Interfaces 2023, 15, 38230–38246. [Google Scholar] [CrossRef] [PubMed]
- Du, E.; Li, X.; He, S.; Li, X.; He, S. The critical role of the interplays of EphrinB2/EphB4 and VEGF in the induction of angiogenesis. Mol. Biol. Rep. 2020, 47, 4681–4690. [Google Scholar] [CrossRef]
- Joussen, A.M.; Ricci, F.; Paris, L.P.; Korn, C.; Quezada-Ruiz, C.; Zarbin, M. Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: A review of preclinical data. Eye 2021, 35, 1305–1316. [Google Scholar] [CrossRef] [PubMed]
- Mckinnirey, F.; Herbert, B.; Vesey, G.; McCracken, S. Immune modulation via adipose derived Mesenchymal Stem cells is driven by donor sex in vitro. Sci. Rep. 2021, 11, 12454. [Google Scholar] [CrossRef]
- Sanjabi, S.; Oh, S.A.; Li, M.O. Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection. Cold Spring Harb. Perspect. Biol. 2017, 9, a022236. [Google Scholar] [CrossRef] [PubMed]
- Johnson, B.Z.; Stevenson, A.W.; Prêle, C.M.; Fear, M.W.; Wood, F.M. The Role of IL-6 in Skin Fibrosis and Cutaneous Wound Healing. Biomedicines 2020, 8, 101. [Google Scholar] [CrossRef] [PubMed]
- Li, D.; Li, X.; Zhang, J.; Tang, Z.; Tian, A. The immunomodulatory effect of IL-4 accelerates bone substitute material-mediated osteogenesis in aged rats via NLRP3 inflammasome inhibition. Front. Immunol. 2023, 14, 1121549. [Google Scholar] [CrossRef]
- Qin, Y.; Ge, G.; Yang, P.; Wang, L.; Qiao, Y.; Pan, G.; Yang, H.; Bai, J.; Cui, W.; Geng, D. An Update on Adipose-Derived Stem Cells for Regenerative Medicine: Where Challenge Meets Opportunity. Adv. Sci. 2023, 10, 2207334. [Google Scholar] [CrossRef]
- Li, X.H.; Chen, F.L.; Shen, H.L. Salidroside promoted osteogenic differentiation of adipose-derived stromal cells through Wnt/β-catenin signaling pathway. J. Orthop. Surg. Res. 2021, 16, 456. [Google Scholar] [CrossRef]
- Rosen, E.D.; Sarraf, P.; Troy, A.E.; Bradwin, G.; Moore, K.; Milstone, D.S.; Spiegelman, B.M.; Mortensen, R.M. PPARγ Is Required for the Differentiation of Adipose Tissue In Vivo and In Vitro. Mol. Cell 1999, 4, 611–617. [Google Scholar] [CrossRef]
- Iyer, S.S.; Cheng, G. Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune Disease. Crit. Rev. Immunol. 2012, 32, 23–63. [Google Scholar] [CrossRef]
- Hu, X.; Li, J.; Fu, M.; Zhao, X.; Wang, W. The JAK/STAT signaling pathway: From bench to clinic. Signal Transduct. Target. Ther. 2021, 6, 402. [Google Scholar] [CrossRef] [PubMed]
- Zha, K.; Tian, Y.; Panayi, A.C.; Mi, B.; Liu, G. Recent Advances in Enhancement Strategies for Osteogenic Differentiation of Mesenchymal Stem Cells in Bone Tissue Engineering. Front. Cell Dev. Biol. 2022, 10, 824812. [Google Scholar] [CrossRef]
- Park, H.-S.; Ju, U.-I.; Park, J.-W.; Song, J.Y.; Shin, D.H.; Lee, K.-H.; Jeong, L.S.; Yu, J.; Lee, H.W.; Cho, J.Y.; et al. PPARγ neddylation essential for adipogenesis is a potential target for treating obesity. Cell Death Differ. 2016, 23, 1296–1311. [Google Scholar] [CrossRef]
- Dong, L.; Li, X.; Leng, W.; Guo, Z.; Cai, T.; Ji, X.; Xu, C.; Zhu, Z.; Lin, J. Adipose stem cells in tissue regeneration and repair: From bench to bedside. Regen. Ther. 2023, 24, 547–560. [Google Scholar] [CrossRef] [PubMed]
- Li, C.; Wei, S.; Xu, Q.; Sun, Y.; Ning, X.; Wang, Z. Application of ADSCs and their Exosomes in Scar Prevention. Stem Cell Rev. Rep. 2022, 18, 952–967. [Google Scholar] [CrossRef] [PubMed]
- Airuddin, S.S.; Halim, A.S.; Wan Sulaiman, W.A.; Kadir, R.; Nasir, N.A.M. Adipose-Derived Stem Cell: “Treat or Trick”. Biomedicines 2021, 9, 1624. [Google Scholar] [CrossRef] [PubMed]
- Lu, P.; Takai, K.; Weaver, V.M.; Werb, Z. Extracellular Matrix Degradation and Remodeling in Development and Disease. Cold Spring Harb. Perspect. Biol. 2011, 3, a005058. [Google Scholar] [CrossRef] [PubMed]
- Lipson, K.E.; Wong, C.; Teng, Y.; Spong, S. CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis. Fibrogenesis Tissue Repair. 2012, 5, S24. [Google Scholar] [CrossRef] [PubMed]
- Xie, C.; Mondal, D.K.; Ulas, M.; Neill, T.; Iozzo, R.V. Oncosuppressive roles of decorin through regulation of multiple receptors and diverse signaling pathways. Am. J. Physiol.-Cell Physiol. 2022, 322, C554–C566. [Google Scholar] [CrossRef] [PubMed]
- Cabral-Pacheco, G.A.; Garza-Veloz, I.; la Rosa, C.C.-D.; Ramirez-Acuña, J.M.; A Perez-Romero, B.; Guerrero-Rodriguez, J.F.; Martinez-Avila, N.; Martinez-Fierro, M.L. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int. J. Mol. Sci. 2020, 21, 9739. [Google Scholar] [CrossRef] [PubMed]
- Zhou, Z.; Chen, Y.; Chai, M.; Tao, R.; Lei, Y.; Jia, Y.; Shu, J.; Ren, J.; Li, G.; Wei, W.; et al. Adipose extracellular matrix promotes skin wound healing by inducing the differentiation of adipose-derived stem cells into fibroblasts. Int. J. Mol. Med. 2019, 43, 890–900. [Google Scholar] [CrossRef] [PubMed]
- Ding, P.; Lu, E.; Li, G.; Sun, Y.; Yang, W.; Zhao, Z. Research Progress on Preparation, Mechanism, and Clinical Application of Nanofat. J. Burn. Care Res. 2022, 43, 1140–1144. [Google Scholar] [CrossRef]
- Fontes, T.; Brandão, I.; Negrão, R.; Martins, M.J.; Monteiro, R. Autologous fat grafting: Harvesting techniques. Ann. Med. Surg. 2018, 36, 212–218. [Google Scholar] [CrossRef]
- Tonnard, P.; Verpaele, A.; Peeters, G.; Hamdi, M.; Cornelissen, M.; Declercq, H. Nanofat Grafting: Basic Research and Clinical Applications. Plast. Reconstr. Surg. 2013, 132, 1017–1026. [Google Scholar] [CrossRef]
- Fotia, C.; Massa, A.; Boriani, F.; Baldini, N.; Granchi, D. Hypoxia enhances proliferation and stemness of human adipose-derived mesenchymal stem cells. Cytotechnology 2015, 67, 1073–1084. [Google Scholar] [CrossRef]
- Eto, H.; Ishimine, H.; Kinoshita, K.; Watanabe-Susaki, K.; Kato, H.; Doi, K.; Kuno, S.; Kurisaki, A.; Yoshimura, K. Characterization of Human Adipose Tissue-Resident Hematopoietic Cell Populations Reveals a Novel Macrophage Subpopulation with CD34 Expression and Mesenchymal Multipotency. Stem Cells Dev. 2013, 22, 985–997. [Google Scholar] [CrossRef] [PubMed]
- Hsiao, S.T.; Lokmic, Z.; Peshavariya, H.; Abberton, K.M.; Dusting, G.J.; Lim, S.Y.; Dilley, R.J. Hypoxic Conditioning Enhances the Angiogenic Paracrine Activity of Human Adipose-Derived Stem Cells. Stem Cells Dev. 2013, 22, 1614–1623. [Google Scholar] [CrossRef] [PubMed]
- Wu, Y.; Chen, L.; Scott, P.G.; Tredget, E.E. Mesenchymal Stem Cells Enhance Wound Healing Through Differentiation and Angiogenesis. Stem Cells 2007, 25, 2648–2659. [Google Scholar] [CrossRef] [PubMed]
- Baptista, L.S.; Do Amaral, R.J.F.C.; Carias, R.B.V.; Aniceto, M.; Claudio-da-Silva, C.; Borojevic, R. An alternative method for the isolation of mesenchymal stromal cells derived from lipoaspirate samples. Cytotherapy 2009, 11, 706–715. [Google Scholar] [CrossRef]
- Condé-Green, A.; Baptista, L.S.; de Amorin, N.F.G.; de Oliveira, E.D.; da Silva, K.R.; Pedrosa, C.D.S.G.; Borojevic, R.; Pitanguy, I. Effects of Centrifugation on Cell Composition and Viability of Aspirated Adipose Tissue Processed for Transplantation. Aesthetic Surg. J. 2010, 30, 249–255. [Google Scholar] [CrossRef] [PubMed]
- Markarian, C.F.; Frey, G.Z.; Silveira, M.D.; Chem, E.M.; Milani, A.R.; Ely, P.B.; Horn, A.P.; Nardi, N.B.; Camassola, M. Isolation of adipose-derived stem cells: A comparison among different methods. Biotechnol. Lett. 2014, 36, 693–702. [Google Scholar] [CrossRef]
- Shah, F.S.; Wu, X.; Dietrich, M.; Rood, J.; Gimble, J.M. A non-enzymatic method for isolating human adipose tissue-derived stromal stem cells. Cytotherapy 2013, 15, 979–985. [Google Scholar] [CrossRef]
- Romanov, Y.u.A.; Darevskaya, A.N.; Merzlikina, N.V.; Buravkova, L.B. Mesenchymal Stem Cells from Human Bone Marrow and Adipose Tissue: Isolation, Characterization, and Differentiation Potentialities. Bull. Exp. Biol. Med. 2005, 140, 138–143. [Google Scholar] [CrossRef]
- Raposio, E.; Caruana, G.; Bonomini, S.; Libondi, G. A Novel and Effective Strategy for the Isolation of Adipose-Derived Stem Cells: Minimally Manipulated Adipose-Derived Stem Cells for More Rapid and Safe Stem Cell Therapy. Plast. Reconstr. Surg. 2014, 133, 1406–1409. [Google Scholar] [CrossRef] [PubMed]
- Prantl, L.; Rennekampff, H.O.; Giunta, R.E.; Harder, Y.; von Heimburg, D.; Heine, N.; Herold, C.; Kneser, U.; Lampert, F.; Machens, H.G.; et al. Aktuelle Erkenntnisse zur Eigenfett Transplantation anhand der neuen Leitlinie “Autologe Fetttransplantation”. Handchir. Mikrochir. Plast. Chir. 2016, 48, 330–336. [Google Scholar] [CrossRef] [PubMed]
- Shauly, O.; Gould, D.J.; Ghavami, A. Fat Grafting: Basic Science, Techniques, and Patient Management. Plast. Reconstr. Surg.—Glob. Open 2022, 10, e3987. [Google Scholar] [CrossRef] [PubMed]
- Gause, T.M.; Kling, R.E.; Sivak, W.N.; Marra, K.G.; Rubin, J.P.; Kokai, L.E. Particle size in fat graft retention: A review on the impact of harvesting technique in lipofilling surgical outcomes. Adipocyte 2014, 3, 273–279. [Google Scholar] [CrossRef] [PubMed]
- Zocchi, M.L.; Vindigni, V.; Pagani, A.; Pirro, O.; Conti, G.; Sbarbati, A.; Bassetto, F. Regulatory, ethical, and technical considerations on regenerative technologies and adipose-derived mesenchymal stem cells. Eur. J. Plast. Surg. 2019, 42, 531–548. [Google Scholar] [CrossRef]
- Uttamani, R.; Venkataram, A.; Venkataram, J.; Mysore, V. Tumescent anesthesia for dermatosurgical procedures other than liposuction. J. Cutan. Aesthet. Surg. 2020, 13, 275. [Google Scholar] [CrossRef]
- Zhang, Q.; Liu, L.N.; Yong, Q.; Deng, J.C.; Cao, W.G. Intralesional injection of adipose-derived stem cells reduces hypertrophic scarring in a rabbit ear model. Stem Cell Res. Ther. 2015, 6, 145. [Google Scholar] [CrossRef] [PubMed]
- Song, J.; Xian, D.; Yang, L.; Xiong, X.; Lai, R.; Zhong, J. Pruritus: Progress toward Pathogenesis and Treatment. BioMed Res. Int. 2018, 2018, 9625936. [Google Scholar] [CrossRef] [PubMed]
- Zocchi, M.L.; Pagani, A. New Strategies in Regenerative Medicine: The Bio-active Composite Grafts. In Plastic and Aesthetic Regenerative Surgery and Fat Grafting; Kalaaji, A., Ed.; Springer International Publishing: Cham, Switzerland, 2022; pp. 221–235. [Google Scholar] [CrossRef]
- Rochette, L.; Mazini, L.; Malka, G.; Zeller, M.; Cottin, Y.; Vergely, C. The Crosstalk of Adipose-Derived Stem Cells (ADSC), Oxidative Stress, and Inflammation in Protective and Adaptive Responses. Int. J. Mol. Sci. 2020, 21, 9262. [Google Scholar] [CrossRef]
- Zocchi, M.L.; Facchin, F.; Pagani, A.; Bonino, C.; Sbarbati, A.; Conti, G.; Vindigni, V.; Bassetto, F. New perspectives in regenerative medicine and surgery: The bioactive composite therapies (BACTs). Eur. J. Plast. Surg. 2022, 45, 1–25. [Google Scholar] [CrossRef]
- Datsi, A.; Steinhoff, M.; Ahmad, F.; Alam, M.; Buddenkotte, J. Interleukin-31: The “itchy” cytokine in inflammation and therapy. Allergy 2021, 76, 2982–2997. [Google Scholar] [CrossRef] [PubMed]
- Hao, Z.; Qi, W.; Sun, J.; Zhou, M.; Guo, N. Review: Research progress of adipose-derived stem cells in the treatment of chronic wounds. Front. Chem. 2023, 11, 1094693. [Google Scholar] [CrossRef]
- Krawczenko, A.; Klimczak, A. Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells and Their Contribution to Angiogenic Processes in Tissue Regeneration. Int. J. Mol. Sci. 2022, 23, 2425. [Google Scholar] [CrossRef] [PubMed]
- Xu, H.; Ni, Y.Q.; Liu, Y.S. Mechanisms of Action of MiRNAs and LncRNAs in Extracellular Vesicle in Atherosclerosis. Front. Cardiovasc. Med. 2021, 8, 733985. [Google Scholar] [CrossRef] [PubMed]
- Ling, L.; Hou, J.; Liu, D.; Tang, D.; Zhang, Y.; Zeng, Q.; Pan, H.; Fan, L. Important role of the SDF-1/CXCR4 axis in the homing of systemically transplanted human amnion-derived mesenchymal stem cells (hAD-MSCs) to ovaries in rats with chemotherapy-induced premature ovarian insufficiency (POI). Stem Cell Res. Ther. 2022, 13, 79. [Google Scholar] [CrossRef]
- Zeng, Z.; Lan, T.; Wei, Y.; Wei, X. CCL5/CCR5 axis in human diseases and related treatments. Genes Dis. 2022, 9, 12–27. [Google Scholar] [CrossRef]
- Furue, M.; Furue, M. Interleukin-31 and Pruritic Skin. JCM 2021, 10, 1906. [Google Scholar] [CrossRef]
- Jia, Q.; Zhao, H.; Wang, Y.; Cen, Y.; Zhang, Z. Mechanisms and applications of adipose-derived stem cell-extracellular vesicles in the inflammation of wound healing. Front. Immunol. 2023, 14, 1214757. [Google Scholar] [CrossRef]
- Xue, Z.; Liao, Y.; Li, Y. Effects of microenvironment and biological behavior on the paracrine function of stem cells. Genes Dis. 2024, 11, 135–147. [Google Scholar] [CrossRef]
- Rautiainen, S.; Laaksonen, T.; Koivuniemi, R. Angiogenic Effects and Crosstalk of Adipose-Derived Mesenchymal Stem/Stromal Cells and Their Extracellular Vesicles with Endothelial Cells. Int. J. Mol. Sci. 2021, 22, 10890. [Google Scholar] [CrossRef]
- Elshaer, S.L.; Bahram, S.H.; Rajashekar, P.; Gangaraju, R.; El-Remessy, A.B. Modulation of Mesenchymal Stem Cells for Enhanced Therapeutic Utility in Ischemic Vascular Diseases. Int. J. Mol. Sci. 2021, 23, 249. [Google Scholar] [CrossRef] [PubMed]
- Brett, E.; Duscher, D.; Pagani, A.; Daigeler, A.; Kolbenschlag, J.; Hahn, M. Naming the Barriers between Anti-CCR5 Therapy, Breast Cancer and Its Microenvironment. Int. J. Mol. Sci. 2022, 23, 14159. [Google Scholar] [CrossRef]
- Turturici, G.; Tinnirello, R.; Sconzo, G.; Geraci, F. Extracellular membrane vesicles as a mechanism of cell-to-cell communication: Advantages and disadvantages. Am. J. Physiol.-Cell Physiol. 2014, 306, C621–C633. [Google Scholar] [CrossRef]
- Sen, C.K.; Ghatak, S. miRNA Control of Tissue Repair and Regeneration. Am. J. Pathol. 2015, 185, 2629–2640. [Google Scholar] [CrossRef] [PubMed]
- Trzyna, A.; Banaś-Ząbczyk, A. Adipose-Derived Stem Cells Secretome and Its Potential Application in “Stem Cell-Free Therapy”. Biomolecules 2021, 11, 878. [Google Scholar] [CrossRef]
- Widgerow, A.D.; Salibian, A.A.; Lalezari, S.; Evans, G.R.D. Neuromodulatory nerve regeneration: Adipose tissue-derived stem cells and neurotrophic mediation in peripheral nerve regeneration. J. Neurosci. Res. 2013, 91, 1517–1524. [Google Scholar] [CrossRef] [PubMed]
- Ohtani, N. The roles and mechanisms of senescence-associated secretory phenotype (SASP): Can it be controlled by senolysis? Inflamm. Regen. 2022, 42, 11. [Google Scholar] [CrossRef] [PubMed]
- Juhl, A.A.; Karlsson, P.; Damsgaard, T.E. Fat grafting for alleviating persistent pain after breast cancer treatment: A randomized controlled trial. J. Plast. Reconstr. Aesthetic Surg. 2016, 69, 1192–1202. [Google Scholar] [CrossRef]
- Kwon, D.G.; Kim, M.K.; Jeon, Y.S.; Nam, Y.C.; Park, J.S.; Ryu, D.J. State of the Art: The Immunomodulatory Role of MSCs for Osteoarthritis. Int. J. Mol. Sci. 2022, 23, 1618. [Google Scholar] [CrossRef]
- Lenzi, L.; Santos, J.; Raduan Neto, J.; Fernandes, C.; Faloppa, F. The Patient and Observer Scar Assessment Scale: Translation for portuguese language, cultural adaptation, and validation. Int. Wound J. 2019, 16, 1513–1520. [Google Scholar] [CrossRef] [PubMed]
- Krastev, T.K.; Schop, S.J.; Hommes, J.; Piatkowski, A.; Van Der Hulst, R.R.W.J. Autologous fat transfer to treat fibrosis and scar-related conditions: A systematic review and meta-analysis. J. Plast. Reconstr. Aesthetic Surg. 2020, 73, 2033–2048. [Google Scholar] [CrossRef]
- Negenborn, V.L.; Groen, J.W.; Smit, J.M.; Niessen, F.B.; Mullender, M.G. The Use of Autologous Fat Grafting for Treatment of Scar Tissue and Scar-Related Conditions: A Systematic Review. Plast. Reconstr. Surg. 2016, 137, 31e–43e. [Google Scholar] [CrossRef] [PubMed]
- Gal, S.; Ramirez, J.I.; Maguina, P. Autologous fat grafting does not improve burn scar appearance: A prospective, randomized, double-blinded, placebo-controlled, pilot study. Burns 2017, 43, 486–489. [Google Scholar] [CrossRef]
- Bassetto, F.; Scarpa, C.; Vindigni, V. Invasive Techniques in Scar Management: Fat Injections. In Textbook on Scar Management; Téot, L., Mustoe, T.A., Middelkoop, E., Gauglitz, G.G., Eds.; Springer International Publishing: Cham, Switzerland, 2020; pp. 333–342. [Google Scholar] [CrossRef]
- Gentile, P.; Orlandi, A.; Scioli, M.G.; Di Pasquali, C.; Bocchini, I.; Curcio, C.B.; Floris, M.; Fiaschetti, V.; Floris, R.; Cervelli, V. A 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. [Google Scholar] [CrossRef] [PubMed]
- Arcuri, F.; Brucoli, M.; Baragiotta, N.; Stellin, L.; Giarda, M.; Benech, A. The Role of Fat Grafting in the Treatment of Posttraumatic Maxillofacial Deformities. Craniomaxillofacial Trauma Reconstr. 2013, 6, 121–125. [Google Scholar] [CrossRef]
- Sterodimas, A.; De Faria, J.; Nicaretta, B.; Boriani, F. Autologous Fat Transplantation Versus Adipose-Derived Stem Cell–Enriched Lipografts: A Study. Aesthetic Surg. J. 2011, 31, 682–693. [Google Scholar] [CrossRef]
- Delay, E.; Garson, S.; Tousson, G.; Sinna, R. Fat Injection to the Breast: Technique, Results, and Indications Based on 880 Procedures Over 10 Years. Aesthetic Surg. J. 2009, 29, 360–376. [Google Scholar] [CrossRef] [PubMed]
- Leong, D.; Hutmacher, D.; Chew, F.; Lim, T. Viability and adipogenic potential of human adipose tissue processed cell population obtained from pump-assisted and syringe-assisted liposuction. J. Dermatol. Sci. 2005, 37, 169–176. [Google Scholar] [CrossRef] [PubMed]
- Nishimura, T.; Hashimoto, H.; Nakanishi, I.; Furukawa, M. Microvascular Angiogenesis and Apoptosis in the Survival of Free Fat Grafts. Laryngoscope 2000, 110, 1333–1338. [Google Scholar] [CrossRef]
- Cervelli, V.; Scioli, M.G.; Gentile, P.; Doldo, E.; Bonanno, E.; Spagnoli, L.G.; Orlandi, A. 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. [Google Scholar] [CrossRef]
- Yoshimura, K.; Sato, K.; Aoi, N.; Kurita, M.; Hirohi, T.; Harii, K. Cell-Assisted Lipotransfer for Cosmetic Breast Augmentation: Supportive Use of Adipose-Derived Stem/Stromal Cells. Aesth Plast. Surg. 2008, 32, 48–55. [Google Scholar] [CrossRef] [PubMed]
- Cervelli, V.; Gentile, P.; Scioli, M.G.; Grimaldi, M.; Casciani, C.U.; Spagnoli, L.G.; Orlandi, A. Application of Platelet-Rich Plasma in Plastic Surgery: Clinical and In Vitro Evaluation. Tissue Eng. Part C Methods 2009, 15, 625–634. [Google Scholar] [CrossRef] [PubMed]
- Klinger, M.; Caviggioli, F.; Klinger, F.M.; Giannasi, S.; Bandi, V.; Banzatti, B.; Forcellini, D.; Maione, L.; Catania, B.; Vinci, V. Autologous Fat Graft in Scar Treatment. J. Craniofacial Surg. 2013, 24, 1610–1615. [Google Scholar] [CrossRef] [PubMed]
- Antar, S.A.; Ashour, N.A.; Marawan, M.E.; Al-Karmalawy, A.A. Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation. Int. J. Mol. Sci. 2023, 24, 4004. [Google Scholar] [CrossRef] [PubMed]
- Klinger, M.; Lisa, A.; Caviggioli, F.; Maione, L.; Murolo, M.; Vinci, V.; Klinger, F.M. Autologous Fat Grafting Improves Facial Nerve Function. Case Rep. Surg. 2015, 2015, 520746. [Google Scholar] [CrossRef] [PubMed]
- Byrne, M.; O’Donnell, M.; Fitzgerald, L.; Shelley, O.P. Early experience with fat grafting as an adjunct for secondary burn reconstruction in the hand: Technique, hand function assessment and aesthetic outcomes. Burns 2016, 42, 356–365. [Google Scholar] [CrossRef]
- Vanderstichele, S.; Vranckx, J.J. Anti-fibrotic effect of adipose-derived stem cells on fibrotic scars. WJSC 2022, 14, 200–213. [Google Scholar] [CrossRef] [PubMed]
- Seo, Y.; Kang, M.J.; Kim, H.S. Strategies to Potentiate Paracrine Therapeutic Efficacy of Mesenchymal Stem Cells in Inflammatory Diseases. Int. J. Mol. Sci. 2021, 22, 3397. [Google Scholar] [CrossRef] [PubMed]
- Ismaeel, A.; Kim, J.S.; Kirk, J.S.; Smith, R.S.; Bohannon, W.T.; Koutakis, P. Role of Transforming Growth Factor-β in Skeletal Muscle Fibrosis: A Review. Int. J. Mol. Sci. 2019, 20, 2446. [Google Scholar] [CrossRef]
- Long, C.; Wang, J.; Gan, W.; Qin, X.; Yang, R.; Chen, X. Therapeutic potential of exosomes from adipose-derived stem cells in chronic wound healing. Front. Surg. 2022, 9, 1030288. [Google Scholar] [CrossRef]
- Yalçın, M.B.; Bora, E.S.; Erdoğan, M.A.; Çakır, A.; Erbaş, O. The Effect of Adipose-Derived Mesenchymal Stem Cells on Peripheral Nerve Damage in a Rodent Model. JCM 2023, 12, 6411. [Google Scholar] [CrossRef] [PubMed]
- Ren, L.L.; Miao, H.; Wang, Y.N.; Liu, F.; Li, P.; Zhao, Y.Y. TGF-β as A Master Regulator of Aging-Associated Tissue Fibrosis. Aging Dis. 2023, 14, 1633. [Google Scholar] [CrossRef]
- Li, Z.-J.; Wang, L.-Q.; Li, Y.-Z.; Wang, C.-Y.; Huang, J.-Z.; Yu, N.-Z.; Long, X. Application of adipose-derived stem cells in treating fibrosis. WJSC 2021, 13, 1747–1761. [Google Scholar] [CrossRef]
- Huang, H.; Shao, L.; Chen, Y.; Tang, L.; Liu, T.; Li, J.; Zhu, H. Synergistic strategy with hyperthermia therapy based immunotherapy and engineered exosomes-liposomes targeted chemotherapy prevents tumor recurrence and metastasis in advanced breast cancer. Bioeng. Transl. Med. 2022, 7, e10284. [Google Scholar] [CrossRef]
- Klinger, M.; Villani, F.; Klinger, F.; Gaetani, P.; Rodriguez YBaena, R.; Levi, D. Anatomical Variations of the Occipital Nerves: Implications for the Treatment of Chronic Headaches. Plast. Reconstr. Surg. 2009, 124, 1727–1728. [Google Scholar] [CrossRef] [PubMed]
- Bathina, S.; Das, U.N. Brain-derived neurotrophic factor and its clinical implications. Arch. Med. Sci. 2015, 6, 1164–1178. [Google Scholar] [CrossRef]
- Dahmani, A.; Delisle, J.S. TGF-β in T Cell Biology: Implications for Cancer Immunotherapy. Cancers 2018, 10, 194. [Google Scholar] [CrossRef]
- Steen, E.H.; Wang, X.; Balaji, S.; Butte, M.J.; Bollyky, P.L.; Keswani, S.G. The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis. Adv. Wound Care 2020, 9, 184–198. [Google Scholar] [CrossRef] [PubMed]
- Travis, M.A.; Sheppard, D. TGF-β Activation and Function in Immunity. Annu. Rev. Immunol. 2014, 32, 51–82. [Google Scholar] [CrossRef]
- Li, Y.; Li, F.; Qin, D.; Chen, H.; Wang, J.; Wang, J.; Song, S.; Wang, C.; Wang, Y.; Liu, S.; et al. The role of brain derived neurotrophic factor in central nervous system. Front. Aging Neurosci. 2022, 14, 986443. [Google Scholar] [CrossRef]
- Palasz, E.; Wilkaniec, A.; Stanaszek, L.; Andrzejewska, A.; Adamczyk, A. Glia-Neurotrophic Factor Relationships: Possible Role in Pathobiology of Neuroinflammation-Related Brain Disorders. Int. J. Mol. Sci. 2023, 24, 6321. [Google Scholar] [CrossRef] [PubMed]
- Le, J.M.; Bosworth, J.W.; Honeywell, B.; Ananthasekar, S.; Collawn, S.S. Adipose Grafting for Volume and Scar Release. Ann. Plast. Surg. 2021, 86, S487–S490. [Google Scholar] [CrossRef] [PubMed]
- El Ayadi, A.; Jay, J.W.; Prasai, A. Current Approaches Targeting the Wound Healing Phases to Attenuate Fibrosis and Scarring. Int. J. Mol. Sci. 2020, 21, 1105. [Google Scholar] [CrossRef] [PubMed]
- Brown, J.C.; Shang, H.; Yang, N.; Pierson, J.; Ratliff, C.R.P.; Prince, N.; Roney, N.; Chan, R.; Hatem, V.; Gittleman, H.; et al. Autologous Fat Transfer for Scar Prevention and Remodeling: A Randomized, Blinded, Placebo-controlled Trial. Plast. Reconstr. Surg.—Glob. Open 2020, 8, e2830. [Google Scholar] [CrossRef]
Techniques and Clinical Implication of Autologous Fat Grafting: Key Points | |
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Overview and Evolution | Autologous adipose tissue is highly accessible, biocompatible, and minimally traumatic surgically. Techniques evolved to use macrofat, microfat, and nanofat for different clinical purposes. |
Macrofat Grafting | Uses particles > 2.4 mm, suitable for large volume augmentations (breasts, buttocks). Requires blunt needles with a 2 mm diameter. |
Microfat Grafting | Uses particles between 1.2 to 2.4 mm, ideal for delicate areas (forehead, eyelids, hands). Smaller particles facilitate smoother injections and detailed enhancements. |
Nanofat Grafting | Involves mechanical emulsification and filtration of microfat. Contains a high concentration of SVF cells and ADSCs, promoting tissue repair and regeneration |
SVF and ADSCs | Vital for graft integration and survival, capable of transforming into mature adipocytes. CD34+ cells within SVF show significant proliferative capabilities and enhance graft viability through angiogenesis. |
Centrifugation process | Critical for isolating the SVF, ensuring optimal regenerative potential. Different mechanical and enzymatic methods impact cell yield and viability. |
Donor Site Selection | No significant difference in fat quality or graft survival among various sites. Selection should consider patient-specific factors and clinical needs. |
Advantages and Limitations | Macrofat is effective for volume but poses embolism risk in superficial tissues. Microfat offers safer and precise enhancements. Nanofat is particularly useful for therapeutic applications such as scar revisions. |
Regenerative Properties | SVF and ADSCs significantly improve skin quality and scar appearance. Enhance tissue repair through angiogenesis, immune modulation, and ECM remodeling. |
Volume Retention | A major challenge, with reductions of up to 70%. Strategies such as cell-assisted lipotransfer (CAL) and PRP aim to improve graft longevity and retention. |
Impact on Fibrosis | AFG reduces fibrosis, improves tissue quality and enhances functional outcomes. ADSCs play a crucial role in mitigating chronic inflammation and promoting angiogenesis. |
Pain Reduction | AFG significantly alleviates pain associated with scar tissue. ADSCs secrete neurotrophic factors such as BDNF, promoting nerve repair and reducing neuropathic pain. |
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Ahmad, N.; Anker, A.; Klein, S.; Dean, J.; Knoedler, L.; Remy, K.; Pagani, A.; Kempa, S.; Terhaag, A.; Prantl, L. Autologous Fat Grafting—A Panacea for Scar Tissue Therapy? Cells 2024, 13, 1384. https://doi.org/10.3390/cells13161384
Ahmad N, Anker A, Klein S, Dean J, Knoedler L, Remy K, Pagani A, Kempa S, Terhaag A, Prantl L. Autologous Fat Grafting—A Panacea for Scar Tissue Therapy? Cells. 2024; 13(16):1384. https://doi.org/10.3390/cells13161384
Chicago/Turabian StyleAhmad, Nura, Alexandra Anker, Silvan Klein, Jillian Dean, Leonard Knoedler, Katya Remy, Andrea Pagani, Sally Kempa, Amraj Terhaag, and Lukas Prantl. 2024. "Autologous Fat Grafting—A Panacea for Scar Tissue Therapy?" Cells 13, no. 16: 1384. https://doi.org/10.3390/cells13161384