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Beneficial Effects of Systemically Administered Human Muse Cells in Adriamycin Nephropathy.
Uchida, Nao; Kushida, Yoshihiro; Kitada, Masaaki; Wakao, Shohei; Kumagai, Naonori; Kuroda, Yasumasa; Kondo, Yoshiaki; Hirohara, Yukari; Kure, Shigeo; Chazenbalk, Gregorio; Dezawa, Mari.
Afiliación
  • Uchida N; Departments of Stem Cell Biology and Histology and.
  • Kushida Y; Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • Kitada M; Departments of Stem Cell Biology and Histology and.
  • Wakao S; Departments of Stem Cell Biology and Histology and.
  • Kumagai N; Departments of Stem Cell Biology and Histology and.
  • Kuroda Y; Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • Kondo Y; Departments of Stem Cell Biology and Histology and.
  • Hirohara Y; Department of Healthcare Services Management, Nihon University School of Medicine, Tokyo, Japan.
  • Kure S; Departments of Stem Cell Biology and Histology and.
  • Chazenbalk G; Regenerative Medicine Division, Life Science Institute, Inc., Tokyo, Japan; and.
  • Dezawa M; Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.
J Am Soc Nephrol ; 28(10): 2946-2960, 2017 Oct.
Article en En | MEDLINE | ID: mdl-28674043
Multilineage-differentiating stress-enduring (Muse) cells are nontumorigenic endogenous pluripotent-like stem cells that can be collected from various organs. Intravenously administered Muse cells have been shown to spontaneously migrate to damaged tissue and replenish lost cells, but the effect in FSGS is unknown. We systemically administered human bone marrow-derived Muse cells without concurrent administration of immunosuppressants to severe combined immune-deficient (SCID) and BALB/c mouse models with adriamycin-induced FSGS (FSGS-SCID and FSGS-BALB/c, respectively). In FSGS-SCID mice, human Muse cells preferentially integrated into the damaged glomeruli and spontaneously differentiated into cells expressing markers of podocytes (podocin; 31%), mesangial cells (megsin; 13%), and endothelial cells (CD31; 41%) without fusing to the host cells; attenuated glomerular sclerosis and interstitial fibrosis; and induced the recovery of creatinine clearance at 7 weeks. Human Muse cells induced similar effects in FSGS-BALB/c mice at 5 weeks, despite xenotransplant without concurrent immunosuppressant administration, and led to improvement in urine protein, creatinine clearance, and plasma creatinine levels more impressive than that in the FSGS-SCID mice at 5 weeks. However, functional recovery in FSGS-BALB/c mice was impaired at 7 weeks due to immunorejection, suggesting the importance of Muse cell survival as glomerular cells in the FSGS kidney for tissue repair and functional recovery. In conclusion, Muse cells are unique reparative stem cells that preferentially home to damaged glomeruli and spontaneously differentiate into glomerular cells after systemic administration. Introduction of genes to induce differentiation is not required before Muse cell administration; thus, Muse cells may be a feasible therapeutic strategy in FSGS.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glomeruloesclerosis Focal y Segmentaria / Trasplante de Células Madre Tipo de estudio: Evaluation_studies Límite: Animals / Humans Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glomeruloesclerosis Focal y Segmentaria / Trasplante de Células Madre Tipo de estudio: Evaluation_studies Límite: Animals / Humans Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos