The influence of combined trophic factors on the success of fetal pancreas grafts

Dev M. Desai, Gregg A. Adams, Xuegong Wang, Edward J. Alfrey, Richard K. Sibley, Donald C. Dafoe

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background. Fetal pancreas (FP) has the capacity for abundant proliferation and beta cell differentiation. Insulin-like growth factor-1 (IGF-1) promotes FP engraftment in the i.m. site and reversal of diabetes in a rodent model. However, reversal of diabetes by an FP transplant in rats under the influence of IGF-1 is still an inefficient process requiring multiple FP grafts and a prolonged latent period. Numerous other growth and differentiation factors, which include platelet derived growth factor (PDGF), vascular endothelial growth factor, endothelial cell growth factor-alpha and pancreatic islet neogenesis-associated protein, have been implicated in beta cell neogenesis and proliferation. We have analyzed the in vivo role of these growth factors in FP engraftment and reversal of streptozotocin-induced diabetes in rats. Methods. IGF-1 alone or in combination with other trophic factors was locally administered to eight FP isografts in the thigh muscle of diabetic rats. Results. Diabetes was reversed in a mean of 60 ± 26 days in 11 of 11 animals treated with IGF-1. PDGF alone did not promote reversal of diabetes; however, PDGF + IGF-1 resulted in euglycemia in 6 of 6, with a mean of 36 ± 14 days (P < 0.05). Islet neogenesis-associated protein + IGF-1 resulted in reversal of diabetes in 6 of 6 rats with a mean interval of 50 ± 10 days. Vascular endothelial growth factor or endothelial cell growth factor-alpha + IGF-1 provided no advantage compared with IGF-1 alone. Conclusions. These results demonstrate that IGF-1 is a potent trophic factor for transplanted FP and that PDGF acts synergistically with IGF-1 to promote reversal of diabetes by transplanting FP.

Original languageEnglish (US)
Pages (from-to)491-496
Number of pages6
JournalTransplantation
Volume68
Issue number4
DOIs
StatePublished - Aug 27 1999

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Somatomedins
Pancreas
Transplants
Platelet-Derived Growth Factor
Endothelial Growth Factors
Vascular Endothelial Growth Factor A
Endothelial Cells
Growth Differentiation Factors
Isografts
Experimental Diabetes Mellitus
Thigh
Islets of Langerhans
Cell Differentiation
Rodentia
Intercellular Signaling Peptides and Proteins
Proteins
Cell Proliferation
Muscles

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

The influence of combined trophic factors on the success of fetal pancreas grafts. / Desai, Dev M.; Adams, Gregg A.; Wang, Xuegong; Alfrey, Edward J.; Sibley, Richard K.; Dafoe, Donald C.

In: Transplantation, Vol. 68, No. 4, 27.08.1999, p. 491-496.

Research output: Contribution to journalArticle

Desai, Dev M. ; Adams, Gregg A. ; Wang, Xuegong ; Alfrey, Edward J. ; Sibley, Richard K. ; Dafoe, Donald C. / The influence of combined trophic factors on the success of fetal pancreas grafts. In: Transplantation. 1999 ; Vol. 68, No. 4. pp. 491-496.
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abstract = "Background. Fetal pancreas (FP) has the capacity for abundant proliferation and beta cell differentiation. Insulin-like growth factor-1 (IGF-1) promotes FP engraftment in the i.m. site and reversal of diabetes in a rodent model. However, reversal of diabetes by an FP transplant in rats under the influence of IGF-1 is still an inefficient process requiring multiple FP grafts and a prolonged latent period. Numerous other growth and differentiation factors, which include platelet derived growth factor (PDGF), vascular endothelial growth factor, endothelial cell growth factor-alpha and pancreatic islet neogenesis-associated protein, have been implicated in beta cell neogenesis and proliferation. We have analyzed the in vivo role of these growth factors in FP engraftment and reversal of streptozotocin-induced diabetes in rats. Methods. IGF-1 alone or in combination with other trophic factors was locally administered to eight FP isografts in the thigh muscle of diabetic rats. Results. Diabetes was reversed in a mean of 60 ± 26 days in 11 of 11 animals treated with IGF-1. PDGF alone did not promote reversal of diabetes; however, PDGF + IGF-1 resulted in euglycemia in 6 of 6, with a mean of 36 ± 14 days (P < 0.05). Islet neogenesis-associated protein + IGF-1 resulted in reversal of diabetes in 6 of 6 rats with a mean interval of 50 ± 10 days. Vascular endothelial growth factor or endothelial cell growth factor-alpha + IGF-1 provided no advantage compared with IGF-1 alone. Conclusions. These results demonstrate that IGF-1 is a potent trophic factor for transplanted FP and that PDGF acts synergistically with IGF-1 to promote reversal of diabetes by transplanting FP.",
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N2 - Background. Fetal pancreas (FP) has the capacity for abundant proliferation and beta cell differentiation. Insulin-like growth factor-1 (IGF-1) promotes FP engraftment in the i.m. site and reversal of diabetes in a rodent model. However, reversal of diabetes by an FP transplant in rats under the influence of IGF-1 is still an inefficient process requiring multiple FP grafts and a prolonged latent period. Numerous other growth and differentiation factors, which include platelet derived growth factor (PDGF), vascular endothelial growth factor, endothelial cell growth factor-alpha and pancreatic islet neogenesis-associated protein, have been implicated in beta cell neogenesis and proliferation. We have analyzed the in vivo role of these growth factors in FP engraftment and reversal of streptozotocin-induced diabetes in rats. Methods. IGF-1 alone or in combination with other trophic factors was locally administered to eight FP isografts in the thigh muscle of diabetic rats. Results. Diabetes was reversed in a mean of 60 ± 26 days in 11 of 11 animals treated with IGF-1. PDGF alone did not promote reversal of diabetes; however, PDGF + IGF-1 resulted in euglycemia in 6 of 6, with a mean of 36 ± 14 days (P < 0.05). Islet neogenesis-associated protein + IGF-1 resulted in reversal of diabetes in 6 of 6 rats with a mean interval of 50 ± 10 days. Vascular endothelial growth factor or endothelial cell growth factor-alpha + IGF-1 provided no advantage compared with IGF-1 alone. Conclusions. These results demonstrate that IGF-1 is a potent trophic factor for transplanted FP and that PDGF acts synergistically with IGF-1 to promote reversal of diabetes by transplanting FP.

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