title: The effects of spheroid formation of adipose-derived stem cells in a microgravity bioreactor on stemness properties and therapeutic potential.
abstract: Adipose-derived stem cells (ADSCs) represent a valuable source of stem cells for regenerative medicine, but the loss of their stemness during in vitro expansion remains a major roadblock. We employed a microgravity bioreactor (MB) to develop a method for biomaterial-free-mediated spheroid formation to maintain the stemness properties of ADSCs. ADSCs spontaneously formed three-dimensional spheroids in the MB. Compared with monolayer culture, the expression levels of E-cadherin and pluripotent markers were significantly upregulated in ADSC spheroids. Spheroid-derived ADSCs exhibited increased proliferative ability and colony-forming efficiency. By culturing the spheroid-derived ADSCs in an appropriate induction medium, we found that the multipotency differentiation capacities of ADSCs were significantly improved by spheroid culture in the MB. Furthermore, when ADSCs were administered to mice with carbon tetrachloride-induced acute liver failure, spheroid-derived ADSCs showed more effective potentials to rescue liver failure than ADSCs derived from constant monolayer culture. Our results suggest that spheroid formation of ADSCs in an MB enhances their stemness properties and increases their therapeutic potential. Therefore, spheroid culture in an MB can be an efficient method to maintain stemness properties, without the involvement of any biomaterials for clinical applications of in vitro cultured ADSCs.
authors.affiliation: Department 4, Institute of Surgery Research, Daping Hospital, Third Military Medical University, State Key Lab of Trauma, Burns and Combined Injury, Chongqing 400042, China.
authors.forename: Shichang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department 4, Institute of Surgery Research, Daping Hospital, Third Military Medical University, State Key Lab of Trauma, Burns and Combined Injury, Chongqing 400042, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210017, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department 4, Institute of Surgery Research, Daping Hospital, Third Military Medical University, State Key Lab of Trauma, Burns and Combined Injury, Chongqing 400042, China.
authors.forename: Zhengguo
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department 4, Institute of Surgery Research, Daping Hospital, Third Military Medical University, State Key Lab of Trauma, Burns and Combined Injury, Chongqing 400042, China. Electronic address: zhangbo67184@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019149:Bioreactors; D019070:Cell Lineage; D049109:Cell Proliferation; D048430:Cell Shape; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D006801:Humans; D008099:Liver / Q000166:cytology; D017114:Liver Failure, Acute / Q000628:therapy; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009474:Neurons / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000378:metabolism; D018874:Spheroids, Cellular / Q000166:cytology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014893:Weightlessness
chemical_list: D015415:Biomarkers
keywords: Adipose-derived stem cells; Microgravity bioreactor; Stemness property; Therapeutic potential