title: Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans.
abstract: Adipose tissue-derived mesenchymal stem cells (AdMSCs) represent an attractive and ethical cell source for stem cell therapy. With the recent demonstration of MSC homing properties, intravenous applications of MSCs to cell-damaged diseases have increased. In the present study, the toxicity and tumorigenicity of human AdMSCs (hAdMSCs) were investigated for clinical application. Culture-expanded hAdMSCs showed the typical appearance, immunophenotype, and differentiation capacity of MSCs, and were genetically stable at least 12 passages in culture. Cells suspended in physiological saline maintained their MSC properties in a cold storage condition for at least 3 days. To test the toxicity of hAdMSCs, different doses of hAdMSCs were injected intravenously into immunodeficient mice, and the mice were observed for 13 weeks. Even at the highest cell dose (2.5×10(8) cells/kg body weight), the SCID mice were viable and had no side effects. A tumorigenicity test was performed in Balb/c-nu nude mice for 26 weeks. Even at the highest cell dose (2×10(8) MSCs/kg), no evidence of tumor development was found. In a human clinical trial, 8 male patients who had suffered a spinal cord injury >12 months previous were intravenously administered autologous hAdMSCs (4×10(8) cells) one time. None of the patients developed any serious adverse events related to hAdMSC transplantation during the 3-month follow-up. In conclusion, the systemic transplantation of hAdMSCs appears to be safe and does not induce tumor development.
authors.affiliation: Stem Cell Research Center, RNL Bio Co, Ltd, Seoul, Republic of Korea. jcra@rnl.co.kr
authors.forename: Jeong Chan
authors.initials: JC
authors.lastname: Ra
authors.forename: Il Seob
authors.initials: IS
authors.lastname: Shin
authors.forename: Sang Han
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung Keun
authors.initials: SK
authors.lastname: Kang
authors.forename: Byeong Cheol
authors.initials: BC
authors.lastname: Kang
authors.forename: Hang Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Youn Joung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Jung Youn
authors.initials: JY
authors.lastname: Jo
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Yoon
authors.forename: Hyung Jun
authors.initials: HJ
authors.lastname: Choi
authors.forename: Euna
authors.initials: E
authors.lastname: Kwon
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000328:Adult; D000818:Animals; D000954:Antigens, Surface; D015197:Carcinogenicity Tests; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D059785:Karyotype; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D008875:Middle Aged; D009369:Neoplasms; D013119:Spinal Cord Injuries / Q000628:therapy*
chemical_list: D000954:Antigens, Surface