title: Skin fibroblasts from patients with type 1 diabetes (T1D) can be chemically transdifferentiated into insulin-expressing clusters: a transgene-free approach.
abstract: The conversion of differentiated cells into insulin-producing cells is a promising approach for the autologous replacement of pancreatic cells in patients with type 1 diabetes (T1D). At present, cellular reprogramming strategies encompass ethical problems, epigenetic failure or teratoma formation, which has prompted the development of new approaches. Here, we report a novel technique for the conversion of skin fibroblasts from T1D patients into insulin-expressing clusters using only drug-based induction. Our results demonstrate that skin fibroblasts from diabetic patients have pancreatic differentiation capacities and avoid the necessity of using transgenic strategies, stem cell sources or global demethylation steps. These findings open new possibilities for studying diabetes mechanisms, drug screenings and ultimately autologous transgenic-free regenerative medicine therapies in patients with T1D.
authors: Instituto de Ciencias Básicas y Medicina Experimental (ICBME), Hospital Italiano de Buenos Aires (HIBA), Buenos Aires, Argentina.
authors: Federico
authors: F
authors: Pereyra-Bonnet
authors: Instituto de Ciencias Básicas y Medicina Experimental (ICBME), Hospital Italiano de Buenos Aires (HIBA), Buenos Aires, Argentina.
authors: María L
authors: ML
authors: Gimeno
authors: Instituto de Ciencias Básicas y Medicina Experimental (ICBME), Hospital Italiano de Buenos Aires (HIBA), Buenos Aires, Argentina.
authors: Nelson R
authors: NR
authors: Argumedo
authors: Instituto de Ciencias Básicas y Medicina Experimental (ICBME), Hospital Italiano de Buenos Aires (HIBA), Buenos Aires, Argentina.
authors: Marcelo
authors: M
authors: Ielpi
authors: Instituto de Ciencias Básicas y Medicina Experimental (ICBME), Hospital Italiano de Buenos Aires (HIBA), Buenos Aires, Argentina.
authors: Johana A
authors: JA
authors: Cardozo
authors: Instituto de Ciencias Básicas y Medicina Experimental (ICBME), Hospital Italiano de Buenos Aires (HIBA), Buenos Aires, Argentina.
authors: Carla A
authors: CA
authors: Giménez
authors: General Surgery Service, HIBA, Buenos Aires, Argentina.
authors: Sung-Ho
authors: SH
authors: Hyon
authors: Endocrinology and Nuclear Medicine Service, HIBA, Buenos Aires, Argentina.
authors: Marta
authors: M
authors: Balzaretti
authors: Instituto de Ciencias Básicas y Medicina Experimental (ICBME), Hospital Italiano de Buenos Aires (HIBA), Buenos Aires, Argentina.
authors: Mónica
authors: M
authors: Loresi
authors: Endocrinology and Nuclear Medicine Service, HIBA, Buenos Aires, Argentina.
authors: Patricia
authors: P
authors: Fainstein-Day
authors: Endocrinology and Nuclear Medicine Service, HIBA, Buenos Aires, Argentina.
authors: León E
authors: LE
authors: Litwak
authors: Instituto de Ciencias Básicas y Medicina Experimental (ICBME), Hospital Italiano de Buenos Aires (HIBA), Buenos Aires, Argentina.
authors: Pablo F
authors: PF
authors: Argibay
mesh_terms: D000293:Adolescent; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects*; D002648:Child; D019175:DNA Methylation / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D006728:Hormones / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology / Q000517:prevention & control; D050417:Insulin-Secreting Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology*; D014158:Transcription, Genetic / Q000187:drug effects; D019737:Transplants
chemical_list: D015415:Biomarkers; D006728:Hormones; D012333:RNA, Messenger