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1. Tesauro P, Trivisonno A, Gennai A, Marliani A, Clauser L; Hair transplantation in cicatricial alopecia: the role of autologous fat transfer; International Journal of Regenerative Medicine, ISSN 2613-5914

2. Martina Rossi; Barbara Roda; Silvia Zia; Ilaria Vigliotta; Chiara Zannini; Francesco Alviano; Laura Bonsi, Andrea Zattoni, Pierluigi Reschiglian, and Alessandro Gennai; Characterisation of the Tissue and Stromal Cell Components of Micro-Superficial Enhanced Fluid Fat Injection (Micro-SEFFI) for Facial Aging Treatment; Aesthetic Surgery Journal 2018, 1–12

3. Tabanella Giorgio, Ferlosio Amedeo, Orlandi Augusto, Gennai Alessandro; Adipose-Derived Mesenchymal Stem Cells Transplantation for Socket Preservation: A Clinical Report; EC Dental Science 18.4 (2019)

4. Gennai A., Bernardini F. P.; Superficial enhanced fluid fat injection (SEFFI and MicroSEFFI) in facial rejuvenation; CellR4 2017; 5 (1): e2239

5. Alessandro Gennai, MD; Alessandra Zambelli, MD; Erica Repaci, PhD; Rodolfo Quarto, MD; Ilaria Baldelli, MD; Giulio Fraternali, PhD; Francesco P. Bernardini, MD; Skin Rejuvenation and Volume Enhancement with the Micro Superficial Enhanced Fluid Fat Injection (M-SEFFI) for Skin Aging of Periocular and Perioral Regions; Aesthetic Surgery Journal 2016, 1–10

6. Francesco P. Bernardini, Alessandro Gennai; Superficial Enhanced Fluid Fat Injection for Volume Restoration and Skin Regeneration of the Periocular Aesthetic Unit. An Improved Fat Grafting Technique to enhance the beauty of the eye; JAMA Plastic Facial Surgery January-February 2016 Vol. 18 n. 1

7. Francesco P. Bernardini, Alessandro Gennai, Luigi Izzo, Alessandra Zambelli, Erica Repaci, Ilaria Baldelli, G. Fraternali-Orcioni, Morris E. Hartstein, Pier Luigi Santi, and Rodolfo Quarto; Superficial Enhanced Fluid Fat Injection (SEFFI) to Correct Volume Defects and Skin Aging of the Face and Periocular Region; Aesthetic Surgery Journal 2015, 1–12

8. Won CH, Park GH, Wu X, Tran TN, Park KY, Park BS, Kim DY, Kwon O, Kim KH; The Basic Mechanism of Hair Growth Stimulation by Adipose-derived Stem Cells and Their Secretory Factors; Curr Stem Cell Res Ther. 2017;12(7):535-543.
Review focused on the effect of ADSCs and their secretory factors on the stimulation of hair growth in vitro, ex vivo and in vivo.
The conditioned media of ADSCs (ADSC-CM) increases the proliferation rate of human follicular cells. ADSCs-derived proteins improve hair growth and protect human dermal papilla cells against cytotoxic injury caused by androgen and reactive oxygen species.
ADSC-CM induces the anagen phase and promotes hair growth in mice, and enhances the elongation of hair shafts in ex vivo human hair organ cultures.

9. Shin H, Won CH, Chung WK, Park BS; Up-to-date Clinical Trials of Hair Regeneration Using Conditioned Media of Adipose-Derived Stem Cells in Male and Female Pattern Hair Loss; Curr Stem Cell Res Ther. 2017;12(7):524-530.
Review on the use of adipose-derived stem cells (ADSCs) on hair regeneration. Besides replacing degenerated cells in affected organs, ADSCs exhibit their beneficial effects through the paracrine actions of various cytokines and growth factors.
Several laboratory experiments and animal studies have shown that ADSC-related proteins can stimulate hair growth. In addition, we introduce our clinical pilot studies using conditioned media of ADSCs for pattern hair loss in men and women, which shown to be a promising alternative therapeutic strategy for hair loss.

10. Shin H, Ryu HH, Kwon O, Park BS, Jo SJ; Clinical use of conditioned media of adipose tissue-derived stem cells in female pattern hair loss: a retrospective case series study; Int J Dermatol. 2015 Jun;54(6):730-5.
Adipose tissue-derived stem cells (ADSCs) and conditioned media of ADSCs (ADSC-CM) are reported to promote hair growth in vitro.
This study evaluates our clinical experience in the use of ADSC-CM for the treatment of FPHL. A retrospective, observational study of outcomes in 27 patients with FPHL treated with ADSC-CM
The application of ADSC-CM showed efficacy in treating FPHL after 12 weeks of therapy. Hair density increased from 105.4 to 122.7 hairs/cm (2) (P < 0.001). Hair thickness increased from 57.5 μm to 64.0 μm (P < 0.001). None of the patients reported severe adverse reactions.

11. Owczarczyk-Saczonek A, Wociór A, Placek W, Maksymowicz W, Wojtkiewicz J.; The Use of Adipose-Derived Stem Cells in Selected Skin Diseases (Vitiligo, Alopecia, and Nonhealing Wounds); Stem Cells Int. 2017;2017:4740709. doi: 10.1155/2017/4740709. Epub 2017 Aug 21.
This article reviews the current data on the use of ADSCs in the treatment of vitiligo, various types of hair loss, and the healing of chronic wounds.

12. Maguire G.; The Safe and Efficacious Use of Secretome From Fibroblasts and Adipose-derived (but not Bone Marrow- derived) Mesenchymal Stem Cells for Skin Therapeutics; J Clin Aesthet Dermatol. 2019 Aug;12(8):E57-E69. Epub 2019 Aug 1.
This review describes the significant advantages of adipose-derived stem cells and fibroblasts in terms of safety and efficacy and compares them to relatively risky platelets and bone marrow stem cells.

13. Butt G, Hussain I, Ahmad FJ, Choudhery MS.; Stromal vascular fraction-enriched platelet-rich plasma therapy reverses the effects of androgenetic alopecia; J Cosmet Dermatol. 2019 Sep 21. doi: 10.1111/jocd.13149. [Epub ahead of print]

14. Won CH, Yoo HG, Kwon OS, Sung MY, Kang YJ, Chung JH, Park BS, Sung JH, Kim WS, Kim KH; Hair growth promoting effects of adipose tissue-derived stem cells; J Dermatol Sci. 2010 Feb;57(2):134-7. doi: 10.1016/j.jdermsci.2009.10.013. Epub 2009 Dec 5.

15. Butt G, Hussain I, Ahmad FJ, Choudhery MS; Stromal vascular fraction-enriched platelet-rich plasma therapy rev.erses the effects of androgenetic alopecia; J Cosmet Dermatol. 2019 Sep 21. doi: 10.1111/jocd.13149. [Epub ahead of print]
BACKGROUND: Since antiquity, humans have been trying to devise remedies to cure androgenetic alopecia (AGA). These efforts include use of oral and topical concoctions and hair transplant strategies. As AGA affects people of all colors and creed, there has been a continuous effort to find a magic bullet against AGA. Unfortunately, to date, all the strategies to negate AGA effects have limitations and thus require new treatment options.
AIM: To evaluate the efficacy of use of stromal vascular fraction (SVF) in androgenetic alopecia patients.
METHODS: Stromal vascular fraction was obtained by enzymatic digestion of autologous adipose tissue. The patients were divided into two groups, that is, platelet-rich plasma (PRP) group and SVF-PRP group. In PRP group, only PRP was injected, while in SVF-PRP group a mixture of PRP and SVF was injected in affected scalp areas. After two sessions (4 weeks apart), the patients in both groups were assessed and analyzed using various parameters.
RESULTS: Mean hair density in PRP group was increased from 52.44 hair/cm2 to 63.72 hair/cm2 (21.51% increase); while in SVF-PRP group, it was 37.66 hair/cm2 before treatment and 57.11 hair/cm2 after SVF-PRP therapy (51.64% increase). Percentage reduction in pull test was more significant in SVF-PRP group (80.78 ± 5.84) as compared to PRP group (34.01 ± 22.44). The physician and patient assessment scores also indicated a significant improvement in SVF-PRP group.
CONCLUSION: A combined SVF-PRP therapy reversed effects of AGA more efficiently as compared to PRP therapy alone.

16. Epstein GK, Epstein JS; Mesenchymal Stem Cells and Stromal Vascular Fraction for Hair Loss: Current Status; Facial Plast Surg Clin North Am. 2018 Nov;26(4):503-511. doi: 10.1016/j.fsc.2018.06.010. Epub 2018 Aug 16.
The current state of the applicability of cell therapy for the treatment of various conditions of hair loss reveals a promising and potentially effective role. Further research, based on published work to date, is indicated to further explore the potential roles of autologous fat grafting, mesenchymal stem cells, and stromal vascular fraction therapy. The authors’ evolving experience matches these promising scientific findings.

17. Stevens HP, Donners S, de Bruijn J.; Introducing Platelet-Rich Stroma: Platelet-Rich Plasma (PRP) and Stromal Vascular Fraction (SVF) Combined for the Treatment of Androgenetic Alopecia; Aesthet Surg J. 2018 Jul 13;38(8):811-822.
BACKGROUND: Androgenetic alopecia (AGA) is characterized by miniaturization of the hair follicles gradually causing conversion of terminal hairs into vellus hairs, leading to progressive reduction of the density of hair on the scalp. Approved therapeutic options are limited and show side effects.
OBJECTIVES: To evaluate injections of stromal vascular fraction (SVF), which is rich in adipose-derived stromal cells (ASCs) in combination with platelet-rich plasma (PRP) in the upper scalp as a new autologous treatment option for AGA.
METHODS: Ten male patients (age range, 25-72 years), suffering from AGA at stage II to III according to the Norwood-Hamilton scale, have been treated with a single injection of autologous PRS (ACPSVF: combination of PRP and SVF) in the upper scalp. Preinjection and 6 and 12 weeks postinjection changes in hair density were assessed using ultra high-resolution photography (Fotofinder).
RESULTS: Hair density was significantly increased after 6 weeks and 12 weeks postinjection (P = 0.013 and P < 0.001). In hair-to-hair matching analyses, new hair grew from active follicles. Furhtermore nonfunctioning hair follicles filled with hyperkeartotic plugs, up to today assumed incapable of forming new hair, proved to grow new hair. No side effects were noted after treatment. CONCLUSIONS: A single treatment of platelet-rich stroma injected in the scalp of patients with AGA significantly increased hair density within 6 to 12 weeks. Further research is required to determine the optimal treatment regimen. Preferred options to our opinion include the repetition of PRS or additional treatments with PRP. 18. Ziering Medical, Marbella, Spain; Ziering Medical, Los Angeles, CA, USA; The Hospital Group, Bromsgrove, Worcestershire, Ziering Medical, Birmingham, Ziering Medical, London, UK, Kerastem Technologies, San Diego, CA, USA; Hair follicle growth by stromal vascular fraction-enhanced adipose transplantation in baldness; Stem Cells Cloning. 2017 Jul 6;10:1-10. doi: 10.2147/SCCAA.S131431. eCollection 2017. Abstract Great interest remains in finding new and emerging therapies for the treatment of male and female pattern hair loss. The autologous fat grafting technique is >100 years old, with a recent and dramatic increase in clinical experience over the past 10-15 years. Recently, in 2001, Zuk et al published the presence of adipose-derived stem cells, and abundant research has shown that adipose is a complex, biological active, and important tissue. Festa et al, in 2011, reported that adipocyte lineage cells support the stem cell niche and help drive the complex hair growth cycle. Adipose-derived regenerative cells (also known as stromal vascular fraction [SVF]) is a heterogeneous group of noncultured cells that can be reliably extracted from adipose by using automated systems, and these cells work largely by paracrine mechanisms to support adipocyte viability. While, today, autologous fat is transplanted primarily for esthetic and reconstructive volume, surgeons have previously reported positive skin and hair changes post-transplantation. This follicular regenerative approach is intriguing and raises the possibility that one can drive or restore the hair cycle in male and female pattern baldness by stimulating the niche with autologous fat enriched with SVF. In this first of a kind patient series, the authors report on the safety, tolerability, and quantitative, as well as photographic changes, in a group of patients with early genetic alopecia treated with subcutaneous scalp injection of enriched adipose tissue. The findings suggest that scalp stem cell-enriched fat grafting may represent a promising alternative approach to treating baldness in men and women.

19. Park BS, Kim WS, Choi JS, Kim HK, Won JH, Ohkubo F, Fukuoka; Hair growth stimulated by conditioned medium of adipose-derived stem cells is enhanced by hypoxia: evidence of increased growth factor secretion; H.Biomed Res. 2010 Feb;31(1):27-34.
Adipose-derived stem cells (ADSCs) and their secretomes mediate diverse skin-regeneration effects, such as wound-healing and antioxidant protection, that are enhanced by hypoxia. We investigated the hair-growth-promoting effect of conditioned medium (CM) of ADSCs to determine if ADSCs and their secretomes regenerate hair and if hypoxia enhances hair regeneration. If so, we wanted to identify the factors responsible for hypoxia-enhanced hair-regeneration. We found that ADSC-CM administrated subcutaneously induced the anagen phase and increased hair regeneration in C(3)H/NeH mice. In addition, ADSC-CM increased the proliferation of human follicle dermal papilla cells (HFDPCs) and human epithelial keratinocytes (HEKs), which are derived from two major cell types present in hair follicles. We investigated the effect of hypoxia on ADSC function using the same animal model in which hypoxia increased hairregrowth. Forty-one growth factors in ADSC-CM from cells cultured under hypoxic or normoxic conditions were analyzed. The secretion of insulin-like growth factor binding protein (IGFBP)-1, IGFBP-2, macrophage colony-stimulating factor (M-CSF), M-CSF receptor, platelet-derived growth factor receptor-beta, and vascular endothelial growth factor was significantly increased by hypoxia, while the secretion of epithelial growth factor production was decreased. It is reasonable to conclude that ADSCs promote hair growth via a paracrine mechanism that is enhanced by hypoxia.

20. Batch JA, Mercuri FA, Werther GA; Identification and localization of insulin-like growth factor-binding protein (IGFBP) messenger RNAs in human hair follicle dermal papilla; J Invest Dermatol. 1996 Mar;106(3):471-5.
The role of the insulin-like growth factors (IGFs) in hair follicle biology has recently been recognized, although their actions, sites of production, and modulation by the insulin-like growth factor-binding proteins (IGFBPs) have not to date been defined. IGF-I is essential for normal hair growth and development, and may be important in regulation of the hair growth cycle. In many culture systems, IGF-I actions are modulated by the IGFBPs. Thus, if IGFBPs are produced in the human hair follicle, they may play a role in targeting IGF-I to its receptor or may modulate IGF-I action by interaction with matrix proteins. We have used in situ hybridization to localize messenger RNA for the six IGFBPs in anagen hair follicles. Anti-sense and sense RNA probes for the IGFBPs (IGFBP-1 to -6) were produced, and 5-micrometer sections of adult facial skin were probed. Messenger RNA for IGFBP-3, -4, and -5 were identified, with predominantly IGFBP-3 and -5 mRNA found in the dermal papilla, and to a lesser extent IGFBP-4 mRNA. IGFBP-4 mRNA was also found at the dermal papilla/epithelial matrix border. Messenger RNAs for both IGFBP-4 and -5 were also demonstrated in the dermal sheath surrounding the hair follicle. Messenger RNAs for IGFBP-1, -2, and -6 were not identified. These studies demonstrate specific localization of IGFBP mRNAs in hair follicles, suggesting that they each play specific roles in the local modulation of IGF action during the hair growth cycle.

21. Elmaadawi IH, Mohamed BM, Ibrahim ZAS, Abdou SM, El Attar YA, Youssef A, Shamloula MM, Taha A, Metwally HG, El Afandy MM, Salem ML; Stem cell therapy as a novel therapeutic intervention for resistant cases of alopecia areata and androgenetic alopecia; J Dermatolog Treat. 2018 Aug;29(5):431-440. doi: 10.1080/09546634.2016.1227419. Epub 2018 Mar 6.
BACKGROUND: Management of alopecia areata (AA) and androgenetic alopecia (AGA) is often challenging as patients may be resistant to currently available modalities of treatment. The use of stem cells may be a novel option for resistant cases.
OBJECTIVE: To evaluate the safety and efficacy of the use of autologous bone marrow derived mononuclear cells(including stem cells) as compared to follicular stems cells for the management of resistant cases of AA and AGA.
METHODS: This study included 40 patients (20 AA patients and 20 AGA patients), all patients were treated with a single session of intradermal injection of autologous stem cells (SCs) therapy. They were divided into four groups according to the applied modality [either autologous bone marrow derived mononuclear cells (bone marrow mononuclear cells [BMMCs] or autologous follicular stem cells [FSC]).
RESULTS: Six months after stem cell therapy (SCT) injection, there was a significant improvement, confirmed by immunostaining and digital dermoscopy. The mean improvement in all groups was “very good”. There was no significant difference between both methods in either type of alopecia. No serious adverse events were reported.
CONCLUSION: Autologous BMMCs and FSC seem to be a safe tolerable and effective treatment for the management of both resistant AA and AGA.

22. A. Gennai, B. Bovani, M. Colli, F. Melfa, D. Piccolo, R. Russo, Barbara Roda, Andrea Zattoni, Pierluigi Reschiglian and Silvia Zia. Comparison of Harvesting and Processing Technique for Adipose Tissue Graft: Evaluation of Cell Viability. Int J Regenr Med doi: 10.31487/j.RGM.2021.02.03 Volume 4(2): 2-5

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