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Stem Cell Therapies for Tissue Regeneration and Wound Healing: Strategies to Enhance Therapeutic Effectiveness

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Regenerative Medicine and Plastic Surgery

Abstract

Stem cells-based therapies remain at the forefront of tissue regeneration, since they represent a unique source of cells endowed with remarkable healing potential. The therapeutic use of progenitor cells for treating chronical wounds has showed promising results in basic science research and preclinical studies. Given their extraordinary characteristics to differentiate and to release cytokines and soluble growth factors, these cells are promising therapeutic sources.

Nevertheless, our current understanding regarding the mechanisms of stem cells-based therapies with regard to complex signaling cascades, environmental influences, or epigenetic modulation is still limited. Here, we present an update on stem cell applications for tissue regeneration, their limitations, specifically in the context of disease states such as aging and diabetes, and novel insights on how to overcome them.

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References

  1. Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014;6(265):265sr6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Ennis WJ, Sui A, Bartholomew A. Stem cells and healing: impact on inflammation. Adv Wound Care. 2013;2(7):369–78.

    Article  Google Scholar 

  3. Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, Gottrup F, Gurtner GC, Longaker MT. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17(6):763–71.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lindholm C, Searle R. Wound management for the 21st century: combining effectiveness and efficiency. Int Wound J. 2016;13(Suppl 2):5–15.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Rando TA. Stem cells, ageing and the quest for immortality. Nature. 2006;441(7097):1080–6.

    Article  CAS  PubMed  Google Scholar 

  6. Werdin F, Tenenhaus M, Rennekampff HO. Chronic wound care. Lancet. 2008;372(9653):1860–2.

    Article  PubMed  Google Scholar 

  7. Reiber GE, Lipsky BA, Gibbons GW. The burden of diabetic foot ulcers. Am J Surg. 1998;176(2A Suppl):5s–10s.

    Article  CAS  PubMed  Google Scholar 

  8. Jain P, Perakath B, Jesudason MR, Nayak S. The effect of autologous bone marrow-derived cells on healing chronic lower extremity wounds: results of a randomized controlled study. Ostomy Wound Manage. 2011;57(7):38–44.

    PubMed  Google Scholar 

  9. Ravari H, Hamidi-Almadari D, Salimifar M, Bonakdaran S, Parizadeh MR, Koliakos G. Treatment of non-healing wounds with autologous bone marrow cells, platelets, fibrin glue and collagen matrix. Cytotherapy. 2011;13(6):705–11.

    Article  CAS  PubMed  Google Scholar 

  10. Otero-Vinas M, Falanga V. Mesenchymal stem cells in chronic wounds: the spectrum from basic to advanced therapy. Adv Wound Care. 2016;5(4):149–63.

    Article  Google Scholar 

  11. Hall PA, Watt FM. Stem cells: the generation and maintenance of cellular diversity. Development. 1989;106(4):619–33.

    Article  CAS  PubMed  Google Scholar 

  12. Odorico JS, Kaufman DS, Thomson JA. Multilineage differentiation from human embryonic stem cell lines. Stem Cells. 2001;19(3):193–204.

    Article  CAS  PubMed  Google Scholar 

  13. Blum B, Benvenisty N. The tumorigenicity of human embryonic stem cells. Adv Cancer Res. 2008;100:133–58.

    Article  PubMed  Google Scholar 

  14. Ben-David U, Benvenisty N. The tumorigenicity of human embryonic and induced pluripotent stem cells. Nat Rev Cancer. 2011;11(4):268–77.

    Article  CAS  PubMed  Google Scholar 

  15. Becker AJ, Mc CE, Till JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature. 1963;197:452–4.

    Article  CAS  PubMed  Google Scholar 

  16. Temple S, Alvarez-Buylla A. Stem cells in the adult mammalian central nervous system. Curr Opin Neurobiol. 1999;9(1):135–41.

    Article  CAS  PubMed  Google Scholar 

  17. Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell. 2004;116(5):639–48.

    Article  CAS  PubMed  Google Scholar 

  18. da Silva ML, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. 2006;119(Pt 11):2204–13.

    Google Scholar 

  19. Marfia G, Navone SE, Di Vito C, Ughi N, Tabano S, Miozzo M, Tremolada C, Bolla G, Crotti C, Ingegnoli F, Rampini P, Riboni L, Gualtierotti R, Campanella R. Mesenchymal stem cells: potential for therapy and treatment of chronic non-healing skin wounds. Organogenesis. 2015;11(4):183–206.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7(2):211–28.

    Article  CAS  PubMed  Google Scholar 

  21. Fuchs E. Skin stem cells: rising to the surface. J Cell Biol. 2008;180(2):273–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bensinger WI, Clift RA, Anasetti C, Appelbaum FA, Demirer T, Rowley S, Appelbaum FR, Benyunes M, Clift R, Martin P, Demirer T, Storb R, Lee M, Schiller G. Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony stimulating factor. Stem Cells. 1996;14(1):90–105.

    Article  CAS  PubMed  Google Scholar 

  23. Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A. 2000;97(25):13625–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gargett CE, Schwab KE, Zillwood RM, Nguyen HP, Wu D. Isolation and culture of epithelial progenitors and mesenchymal stem cells from human endometrium. Biol Reprod. 2009;80(6):1136–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, Fu YS, Lai MC, Chen CC. Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord. Stem Cells. 2004;22(7):1330–7.

    Article  PubMed  Google Scholar 

  26. Jordan CT, Guzman ML, Noble M. Cancer stem cells. N Engl J Med. 2006;355(12):1253–61.

    Article  CAS  PubMed  Google Scholar 

  27. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop DJ, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–7.

    Article  CAS  PubMed  Google Scholar 

  28. Phinney DG, Prockop DJ. Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair--current views. Stem Cells. 2007;25(11):2896–902.

    Article  PubMed  Google Scholar 

  29. Hocking AM. Mesenchymal stem cell therapy for cutaneous wounds. Adv Wound Care. 2012;1(4):166–71.

    Article  Google Scholar 

  30. Sasaki M, Abe R, Fujita Y, Ando S, Inokuma D, Shimizu H. Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. J Immunol. 2008;180(4):2581–7.

    Article  CAS  PubMed  Google Scholar 

  31. Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol. 2007;127(3):514–25.

    Article  CAS  PubMed  Google Scholar 

  32. Nuschke A. Activity of mesenchymal stem cells in therapies for chronic skin wound healing. Organogenesis. 2014;10(1):29–37.

    Article  PubMed  Google Scholar 

  33. Park SR, Kim JW, Jun HS, Roh JY, Lee HY, Hong IS. Stem cell secretome and its effect on cellular mechanisms relevant to wound healing. Mol Ther. 2018;26(2):606–17.

    Article  CAS  PubMed  Google Scholar 

  34. Park BS, Jang KA, Sung JH, Park JS, Kwon YH, Kim KJ, Kim WS. Adipose-derived stem cells and their secretory factors as a promising therapy for skin aging. Dermatol Surg. 2008;34(10):1323–6.

    CAS  PubMed  Google Scholar 

  35. Kapur SK, Katz AJ. Review of the adipose derived stem cell secretome. Biochimie. 2013;95(12):2222–8.

    Article  CAS  PubMed  Google Scholar 

  36. Kober J, Gugerell A, Schmid M, Zeyda M, Buchberger E, Nickl S, Hacker S, Ankersmit HJ, Keck M. Wound healing effect of conditioned media obtained from adipose tissue on human skin cells: a comparative in vitro study. Ann Plast Surg. 2016;77(2):156–63.

    Article  CAS  PubMed  Google Scholar 

  37. Cerqueira MT, Pirraco RP, Marques AP. Stem cells in skin wound healing: are we there yet? Adv Wound Care. 2016;5(4):164–75.

    Article  Google Scholar 

  38. Jayaraman P, Nathan P, Vasanthan P, Musa S, Govindasamy V. Stem cells conditioned medium: a new approach to skin wound healing management. Cell Biol Int. 2013;37(10):1122–8.

    Article  PubMed  Google Scholar 

  39. Na YK, Ban JJ, Lee M, Im W, Kim M. Wound healing potential of adipose tissue stem cell extract. Biochem Biophys Res Commun. 2017;485(1):30–4.

    Article  CAS  PubMed  Google Scholar 

  40. Krasnodembskaya A, Song Y, Fang X, Gupta N, Serikov V, Lee JW, Matthay MA. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells. 2010;28(12):2229–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mei SH, Haitsma JJ, Dos Santos CC, Deng Y, Lai PF, Slutsky AS, Liles WC, Stewart DJ. l. Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis. Am J Respir Crit Care Med. 2010;182(8):1047–57.

    Article  CAS  PubMed  Google Scholar 

  42. Friedenstein AJ, Piatetzky S II, Petrakova KV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol. 1966;16(3):381–90.

    CAS  PubMed  Google Scholar 

  43. Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol. 1966;16(3):381–90.

    CAS  PubMed  Google Scholar 

  44. Friedenstein AJ. Stromal mechanisms of bone marrow: cloning in vitro and retransplantation in vivo. Haematol Blood Transfus. 1980;25:19–29.

    CAS  PubMed  Google Scholar 

  45. Owen M, Friedenstein AJ. Stromal stem cells: marrow-derived osteogenic precursors. Ciba Found Symp. 1988;136:42–60.

    CAS  PubMed  Google Scholar 

  46. Grigoriadis AE, Heersche JN, Aubin JE. Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone-derived clonal cell population: effect of dexamethasone. J Cell Biol. 1988;106(6):2139–51.

    Article  CAS  PubMed  Google Scholar 

  47. Wakitani S, Saito T, Caplan AI. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve. 1995;18(12):1417–26.

    Article  CAS  PubMed  Google Scholar 

  48. Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, Mavilio F. Muscle regeneration by bone marrow-derived myogenic progenitors. Science. 1998;279(5356):1528–30.

    Article  CAS  PubMed  Google Scholar 

  49. Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res. 1998;238(1):265–72.

    Article  CAS  PubMed  Google Scholar 

  50. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–7.

    Article  CAS  PubMed  Google Scholar 

  51. Arici V, Perotti C, Fabrizio C, Del Fante C, Ragni F, Alessandrino F, Viarengo G, Pagani M, Moia A, Tinelli C, Bozzani A. Autologous immuno magnetically selected CD133+ stem cells in the treatment of no-option critical limb ischemia: clinical and contrast enhanced ultrasound assessed results in eight patients. J Transl Med. 2015;13:342.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Kirana S, Stratmann B, Prante C, Prohaska W, Koerperich H, Lammers D, Gastens MH, Quast T, Negrean M, Stirban OA, Nandrean SG, Götting C, Minartz P, Kleesiek K, Tschoepe D. Autologous stem cell therapy in the treatment of limb ischaemia induced chronic tissue ulcers of diabetic foot patients. Int J Clin Pract. 2012;66(4):384–93.

    Article  CAS  PubMed  Google Scholar 

  53. Kirana S, Stratmann B, Lammers D, Negrean M, Stirban A, Minartz P, Koerperich H, Gastens MH, Götting C, Prohaska W, Kleesiek K, Tschoepe D. Wound therapy with autologous bone marrow stem cells in diabetic patients with ischaemia-induced tissue ulcers affecting the lower limbs. Int J Clin Pract. 2007;61(4):690–2.

    Article  CAS  PubMed  Google Scholar 

  54. Klepanec A, Mistrik M, Altaner C, Valachovicova M, Olejarova I, Slysko R, Balazs T, Urlandova T, Hladikova D, Liska B, Tomka J, Vulev I, Madaric J. No difference in intra-arterial and intramuscular delivery of autologous bone marrow cells in patients with advanced critical limb ischemia. Cell Transpl. 2012;21(9):1909–18.

    Article  Google Scholar 

  55. Yoshikawa T, Mitsuno H, Nonaka I, Sen Y, Kawanishi K, Inada Y, Takakura Y, Okuchi K, Nonomura A. Wound therapy by marrow mesenchymal cell transplantation. Plast Reconstr Surg. 2008;121(3):860–77.

    Article  CAS  PubMed  Google Scholar 

  56. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Sekiya I, Larson BL, Smith JR, Pochampally R, Cui JG, Prockop DJ. Expansion of human adult stem cells from bone marrow stroma: conditions that maximize the yields of early progenitors and evaluate their quality. Stem Cells. 2002;20(6):530–41.

    Article  PubMed  Google Scholar 

  58. Hausman GJ. Techniques for studying adipocytes. Stain Technol. 1981;56(3):149–54.

    Article  CAS  PubMed  Google Scholar 

  59. Pettersson P, Cigolini M, Sjostrom L, Smith U, Bjorntorp P. Cells in human adipose tissue developing into adipocytes. Acta Med Scand. 1984;215(5):447–51.

    Article  CAS  PubMed  Google Scholar 

  60. Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP, Yoshimura K, Gimble JM. 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). Cytotherapy. 2013;15(6):641–8.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Astori G, Vignati F, Bardelli S, Tubio M, Gola M, Albertini V, Bambi F, Scali G, Castelli D, Rasini V, Soldati G, Moccetti T. “In vitro” and multicolor phenotypic characterization of cell subpopulations identified in fresh human adipose tissue stromal vascular fraction and in the derived mesenchymal stem cells. J Transl Med. 2007;5:55.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Strutt B, Khalil W, Killinger D. Growth and differentiation of human adipose stromal cells in culture. Meth Mol Med. 1996;2:41–51.

    CAS  Google Scholar 

  63. Gronthos S, Franklin DM, Leddy HA, Robey PG, Storms RW, Gimble JM. Surface protein characterization of human adipose tissue-derived stromal cells. J Cell Physiol. 2001;189(1):54–63.

    Article  CAS  PubMed  Google Scholar 

  64. Musina RA, Bekchanova ES, Sukhikh GT. Comparison of mesenchymal stem cells obtained from different human tissues. Bull Exp Biol Med. 2005;139(4):504–9.

    Article  CAS  PubMed  Google Scholar 

  65. Ashjian PH, Elbarbary AS, Edmonds B, DeUgarte D, Zhu M, Zuk PA, Lorenz HP, Benhaim P, Hedrick MH. In vitro differentiation of human processed lipoaspirate cells into early neural progenitors. Plast Reconstr Surg. 2003;111(6):1922–31.

    Article  PubMed  Google Scholar 

  66. Trottier V, Marceau-Fortier G, Germain L, Vincent C, Fradette J. IFATS collection: using human adipose-derived stem/stromal cells for the production of new skin substitutes. Stem Cells. 2008;26(10):2713–23.

    Article  PubMed  Google Scholar 

  67. Seo MJ, Suh SY, Bae YC, Jung JS. Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun. 2005;328(1):258–64.

    Article  CAS  PubMed  Google Scholar 

  68. Kim WS, Park BS, Sung JH, Yang JM, Park SB, Kwak SJ, Park JS. Wound healing effect of adipose-derived stem cells: a critical role of secretory factors on human dermal fibroblasts. J Derm Sci. 2007;48(1):15–24.

    Article  CAS  Google Scholar 

  69. Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE, Pell CL, Johnstone BH, Considine RV, March KL. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation. 2004;109(10):1292–8.

    Article  PubMed  Google Scholar 

  70. Nie C, Yang D, Xu J, Si Z, Jin X, Zhang J. Locally administered adipose-derived stem cells accelerate wound healing through differentiation and vasculogenesis. Cell Transpl. 2011;20(2):205–16.

    Article  Google Scholar 

  71. Salgado AJ, Reis RL, Sousa NJ, Gimble JM. Adipose tissue derived stem cells secretome: soluble factors and their roles in regenerative medicine. Curr Stem Cell Res Ther. 2010;5(2):103–10.

    Article  CAS  PubMed  Google Scholar 

  72. Hassan WU, Greiser U, Wang W. Role of adipose-derived stem cells in wound healing. Wound Repair Regen. 2014;22(3):313–25.

    Article  PubMed  Google Scholar 

  73. Bura A, Planat-Benard V, Bourin P, Silvestre JS, Gross F, Grolleau JL, Saint-Lebese B, Peyrafitte JA, Fleury S, Gadelorge M, Taurand M, Dupuis-Coronas S, Leobon B, Casteilla L. Phase I trial: the use of autologous cultured adipose-derived stroma/stem cells to treat patients with non-revascularizable critical limb ischemia. Cytotherapy. 2014;16(2):245–57.

    Article  CAS  PubMed  Google Scholar 

  74. Yoshimura K, Suga H, Eto H. Adipose-derived stem/progenitor cells: roles in adipose tissue remodeling and potential use for soft tissue augmentation. Regen Med. 2009;4(2):265–73.

    Article  PubMed  Google Scholar 

  75. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453(7193):314–21.

    Article  CAS  PubMed  Google Scholar 

  76. Hu MS, Leavitt T, Malhotra S, Duscher D, Pollhammer MS, Walmsley GG, Maan ZN, Cheung AT, Schmidt M, Huemer GM, Longaker MT, Lorenz HP. Stem cell-based therapeutics to improve wound healing. Plast Surg Int. 2015;2015:383581.

    PubMed  PubMed Central  Google Scholar 

  77. Whittam AJ, Maan ZN, Duscher D, Wong VW, Barrera JA, Januszyk M, Gurtner GC. Challenges and opportunities in drug delivery for wound healing. Adv Wound Care. 2016;5(2):79–88.

    Article  Google Scholar 

  78. Rennert RC, Sorkin M, Januszyk M, Duscher D, Kosaraju R, Chung MT, Lennon J, Radiya-Dixit A, Raghvendra S, Maan ZN, Hu MS, Rajadas J, Rodrigues M, Gurtner GC. Diabetes impairs the angiogenic potential of adipose-derived stem cells by selectively depleting cellular subpopulations. Stem Cell Res Ther. 2014;5(3):79.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Falanga V. Wound healing and its impairment in the diabetic foot. Lancet. 2005;366(9498):1736–43.

    Article  PubMed  Google Scholar 

  80. Trengove NJ, Stacey MC, Macauley S, Bennett N, Gibson J, Burslem F, Murphy G, Schultz G. Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors. Wound Repair Regen. 1999;7(6):442–52.

    Article  CAS  PubMed  Google Scholar 

  81. Koenen P, Spanholtz TA, Maegele M, Sturmer E, Brockamp T, Neugebauer E, Thamm OC. Acute and chronic wound fluids inversely influence adipose-derived stem cell function: molecular insights into impaired wound healing. Int Wound J. 2015;12(1):10–6.

    Article  PubMed  Google Scholar 

  82. Cianfarani F, Toietta G, Di Rocco G, Cesareo E, Zambruno G, Odorisio T. Diabetes impairs adipose tissue-derived stem cell function and efficiency in promoting wound healing. Wound Rep Regen. 2013;21(4):545–53.

    Article  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Duscher D, Barrera J, Wong VW, Maan ZN, Whittam AJ, Januszyk M, Gurtner GC. Stem cells in wound healing: the future of regenerative medicine? Mini-Rev Gerontol. 2016;62(2):216–25.

    Article  CAS  Google Scholar 

  85. Duscher D, Rennert RC, Januszyk M, Anghel E, Maan ZN, Whittam AJ, Perez MG, Kosaraju R, Hu MS, Walmsley GG, Atashroo D, Khong S, Butte AJ, Gurtner GC. Aging disrupts cell subpopulation dynamics and diminishes the function of mesenchymal stem cells. Sci Rep. 2014;4:7144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Fisher C, Grahovac TL, Schafer ME, Shippert RD, Marra KG, Rubin JP. Comparison of harvest and processing techniques for fat grafting and adipose stem cell isolation. Plast Reconstr Surg. 2013;132(2):351–61.

    Article  CAS  PubMed  Google Scholar 

  87. Shridharani SM, Broyles JM, Matarasso A. Liposuction devices: technology update. Med Dev. 2014;7:241–51.

    Google Scholar 

  88. Duscher D, Luan A, Rennert RC, Atashroo D, Maan ZN, Brett EA, Whittam AJ, Ho N, Lin M, Hu MS, Walmsley GG, Wenny R, Schmidt M, Schilling AF, Machens HG, Huemer GM, Wan DC, Longaker MT, Gurtner GC. Suction assisted liposuction does not impair the regenerative potential of adipose derived stem cells. J Transl Med. 2016;14(1):126.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Duscher D, Maan ZN, Luan A, Aitzetmuller MM, Brett EA, Atashroo D, Whittam AJ, Hu MS, Walmsley GG, Houschyar KS, Schilling AF, Machens HG, Gurtner GC, Longaker MT, Wan DC. Ultrasound-assisted liposuction provides a source for functional adipose-derived stromal cells. Cytotherapy. 2017;19(12):1491–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Januszyk M, Gurtner GC. High-throughput single-cell analysis for wound healing applications. Adv Wound Care. 2013;2(9):457–69.

    Article  Google Scholar 

  91. Rennert RC, Januszyk M, Sorkin M, Rodrigues M, Maan ZN, Duscher D, Whittam AJ, Kosaraju R, Chung MT, Paik K, Li AY, Findlay M, Glotzbach JP, Butte AJ, Gurtner GC. Microfluidic single-cell transcriptional analysis rationally identifies novel surface marker profiles to enhance cell-based therapies. Nat Commun. 2016;7:11945.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Grayson WL, Zhao F, Bunnell B, Ma T. Hypoxia enhances proliferation and tissue formation of human mesenchymal stem cells. Biochem Biophys Res Commun. 2007;358(3):948–53.

    Article  CAS  PubMed  Google Scholar 

  93. Lee EY, Xia Y, Kim WS, Kim MH, Kim TH, Kim KJ, Park BS, Sung JH. Hypoxia-enhanced wound-healing function of adipose-derived stem cells: increase in stem cell proliferation and up-regulation of VEGF and bFGF. Wound Repair Regen. 2009;17(4):540–7.

    Article  PubMed  Google Scholar 

  94. Rubina K, Kalinina N, Efimenko A, Lopatina T, Melikhova V, Tsokolaeva Z, Sysoeva V, Tkachuk V, Parfyonova Y. Adipose stromal cells stimulate angiogenesis via promoting progenitor cell differentiation, secretion of angiogenic factors, and enhancing vessel maturation. Tissue Eng Part A. 2009;15(8):2039–50.

    Article  CAS  PubMed  Google Scholar 

  95. Richmond NA, Lamel SA, Davidson JM, Martins-Green M, Sen CK, Tomic-Canic M, Vivas AC, Braun LR, Kirsner RS. US-National Institutes of Health-funded research for cutaneous wounds in 2012. Wound Repair Regen. 2013;21(6):789–92.

    Article  PubMed  Google Scholar 

  96. Altman AM, Matthias N, Yan Y, Song YH, Bai X, Chiu ES, Slakey DP, Alt EU. Dermal matrix as a carrier for in vivo delivery of human adipose-derived stem cells. Biomaterials. 2008;29(10):1431–42.

    Article  CAS  PubMed  Google Scholar 

  97. Rustad KC, Wong VW, Sorkin M, Glotzbach JP, Major MR, Rajadas J, Longaker MT, Gurtner GC. Enhancement of mesenchymal stem cell angiogenic capacity and stemness by a biomimetic hydrogel scaffold. Biomaterials. 2012;33(1):80–90.

    Article  CAS  PubMed  Google Scholar 

  98. Garg RK, Rennert RC, Duscher D, Sorkin M, Kosaraju R, Auerbach LJ, Lennon J, Chung MT, Paik K, Nimpf J, Rajadas J, Longaker MT, Gurtner GC. Capillary force seeding of hydrogels for adipose-derived stem cell delivery in wounds. Stem Cells Transl Med. 2014;3(9):1079–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Alvarez Garcia J, Garcia Gomez-Heras S, Riera Del Moral L, Largo C, Garcia-Olmo D, Garcia-Arranz M. The effects of allogenic stem cells in a murine model of hind limb diabetic ischemic tissue. Peer J. 2017;5:e3664.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Puissant B, Barreau C, Bourin P, Clavel C, Corre J, Bousquet C, Taureau C, Cousin B, Abbal M, Laharrague P, Penicaud L, Casteilla L, Blancher A. Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells. Br J Haematol. 2005;129(1):118–29.

    Article  PubMed  Google Scholar 

  101. Lin CS, Lin G, Lue TF. Allogeneic and xenogeneic transplantation of adipose-derived stem cells in immunocompetent recipients without immunosuppressants. Stem Cells Dev. 2012;21(15):2770–8.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76.

    Article  CAS  PubMed  Google Scholar 

  103. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917–20.

    Article  CAS  PubMed  Google Scholar 

  104. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–72.

    Article  CAS  PubMed  Google Scholar 

  105. Takahashi K, Okita K, Nakagawa M, Yamanaka S. Induction of pluripotent stem cells from fibroblast cultures. Nat Protoc. 2007;2(12):3081–9.

    Article  CAS  PubMed  Google Scholar 

  106. Itoh M, Umegaki-Arao N, Guo Z, Liu L, Higgins CA, Christiano AM. Generation of 3D skin equivalents fully reconstituted from human induced pluripotent stem cells (iPSCs). PLoS One. 2013;8(10):e77673.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Sebastiano V, Zhen HH, Haddad B, Bashkirova E, Melo SP, Wang P, Leung TL, Siprashvili Z, Tichy A, Li J, Ameen M, Hawkins J, Lee S, Li L, Schwertschkow A, Bauer G, Lisowski L, Kay MA, Kim SK, Lane AT, Wernig M, Oro AE. Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa. Sci Transl Med. 2014;6(264):264ra163.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Hewitt KJ, Shamis Y, Hayman RB, Margvelashvili M, Dong S, Carlson MW, Garlick JA. Epigenetic and phenotypic profile of fibroblasts derived from induced pluripotent stem cells. PLoS One. 2011;6(2):e17128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Yang R, Zheng Y, Burrows M, Liu S, Wei Z, Nace A, Guo W, Kumar S, Cotsarelis G, Xu X. Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells. Nat Commun. 2014;5:3071.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division for Experimental Plastic Surgery, Department of Plastic and Hand Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

    Silvia Mihalceanu, Matthias M. Aitzetmüller & Hans-Günther Machens

  2. Department for Plastic Surgery and Hand Surgery, Division of Experimental Plastic Surgery, Technical University of Munich, Munich, Germany

    Dominik Duscher

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  1. Silvia Mihalceanu
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  2. Matthias M. Aitzetmüller
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  3. Hans-Günther Machens
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  4. Dominik Duscher
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Editors and Affiliations

  1. Department for Plastic Surgery and Hand Surgery, Division of Experimental Plastic Surgery, Technical University of Munich, Munich, Germany

    Dominik Duscher

  2. Private Practice, Tustin, CA, USA

    Melvin A. Shiffman

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Mihalceanu, S., Aitzetmüller, M.M., Machens, HG., Duscher, D. (2019). Stem Cell Therapies for Tissue Regeneration and Wound Healing: Strategies to Enhance Therapeutic Effectiveness. In: Duscher, D., Shiffman, M.A. (eds) Regenerative Medicine and Plastic Surgery. Springer, Cham. https://doi.org/10.1007/978-3-030-19958-6_18

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