title: Pancreatic-derived pathfinder cells enable regeneration of critically damaged adult pancreatic tissue and completely reverse streptozotocin-induced diabetes.
abstract: We demonstrate that intravenous delivery of human, or rat, pancreas-derived pathfinder (PDP) cells can totally regenerate critically damaged adult tissue and restore normal function across a species barrier. We have used a mouse model of streptozotocin (STZ)-induced diabetes to demonstrate this. Normoglycemia was restored and maintained for up to 89 days following the induction of diabetes and subsequent intravenous delivery of PDP cells. Normal pancreatic histology also appeared to be restored, and treated diabetic animals gained body weight. Regenerated tissue was primarily of host origin, with few rat or human cells detectable by fluorescent in situ hybridization (FISH). Crucially, the insulin produced by these animals was overwhelmingly murine in origin and was both types I and II, indicative of a process of developmental recapitulation. These results demonstrate the feasibility of using intravenous administration of adult cells to regenerate damaged tissue. Critically, they enhance our understanding of the mechanisms relating to such repair and suggest a means for novel therapeutic intervention in loss of tissue and organ function with age.
authors.affiliation: University of Glasgow, Institute of Cancer Sciences, Western Infirmary Glasgow, Glasgow, United Kingdom.
authors.forename: Karen
authors.initials: K
authors.lastname: Stevenson
authors.forename: Daxin
authors.initials: D
authors.lastname: Chen
authors.forename: Alan
authors.initials: A
authors.lastname: MacIntyre
authors.forename: Liane M
authors.initials: LM
authors.lastname: McGlynn
authors.forename: Paul
authors.initials: P
authors.lastname: Montague
authors.forename: Rawiya
authors.initials: R
authors.lastname: Charif
authors.forename: Murali
authors.initials: M
authors.lastname: Subramaniam
authors.forename: W D
authors.initials: WD
authors.lastname: George
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Payne
authors.forename: R Wayne
authors.initials: RW
authors.lastname: Davies
authors.forename: Anthony
authors.initials: A
authors.lastname: Dorling
authors.forename: Paul G
authors.initials: PG
authors.lastname: Shiels
mesh_terms: D000328:Adult; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000166:cytology* / Q000473:pathology / Q000502:physiology*; D051381:Rats; D012038:Regeneration; D033581:Stem Cell Transplantation