Valentina Villani1, Anna Milanesi2, Sargis Sedrakyan1, Stefano Da Sacco1, Susanne Angelow1, Maria Teresa Conconi3, Rosa Di Liddo3, Roger De Filippo1, Laura Perin4. 1. Department of Urology, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California. 2. Division of Endocrinology, VA Greater Los Angeles Healthcare System, University of California Los Angeles, Los Angeles, California. 3. Department of Pharmaceutical Sciences, University of Padua, Padua, Italy. 4. Department of Urology, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California. Electronic address: lperin@chla.usc.edu.
Abstract
BACKGROUND AIMS: The contribution of amniotic fluid stem cells (AFSC) to tissue protection and regeneration in models of acute and chronic kidney injuries and lung failure has been shown in recent years. In the present study, we used a chemically induced mouse model of type 1 diabetes to determine whether AFSC could play a role in modulating β-cell injury and restoring β-cell function. METHODS: Streptozotocin-induced diabetic mice were given intracardial injection of AFSC; morphological and physiological parameters and gene expression profile for the insulin pathway were evaluated after cell transplantation. RESULTS: AFSC injection resulted in protection from β-cell damage and increased β-cell regeneration in a subset of mice as indicated by glucose and insulin levels, increased islet mass and preservation of islet structure. Moreover, β-cell preservation/regeneration correlated with activation of the insulin receptor/Pi3K/Akt signaling pathway and vascular endothelial growth factor-A expression involved in maintaining β-cell mass and function. CONCLUSIONS: Our results suggest a therapeutic role for AFSC in preserving and promoting endogenous β-cell functionality and proliferation. The protective role of AFSC is evident when stem cell transplantation is performed before severe hyperglycemia occurs, which suggests the importance of early intervention. The present study demonstrates the possible benefits of the application of a non-genetically engineered stem cell population derived from amniotic fluid for the treatment of type 1 diabetes mellitus and gives new insight on the mechanism by which the beneficial effect is achieved.
BACKGROUND AIMS: The contribution of amniotic fluid stem cells (AFSC) to tissue protection and regeneration in models of acute and chronic kidney injuries and lung failure has been shown in recent years. In the present study, we used a chemically induced mouse model of type 1 diabetes to determine whether AFSC could play a role in modulating β-cell injury and restoring β-cell function. METHODS:Streptozotocin-induced diabeticmice were given intracardial injection of AFSC; morphological and physiological parameters and gene expression profile for the insulin pathway were evaluated after cell transplantation. RESULTS: AFSC injection resulted in protection from β-cell damage and increased β-cell regeneration in a subset of mice as indicated by glucose and insulin levels, increased islet mass and preservation of islet structure. Moreover, β-cell preservation/regeneration correlated with activation of the insulin receptor/Pi3K/Akt signaling pathway and vascular endothelial growth factor-A expression involved in maintaining β-cell mass and function. CONCLUSIONS: Our results suggest a therapeutic role for AFSC in preserving and promoting endogenous β-cell functionality and proliferation. The protective role of AFSC is evident when stem cell transplantation is performed before severe hyperglycemia occurs, which suggests the importance of early intervention. The present study demonstrates the possible benefits of the application of a non-genetically engineered stem cell population derived from amniotic fluid for the treatment of type 1 diabetes mellitus and gives new insight on the mechanism by which the beneficial effect is achieved.
Authors: Gianni Carraro; Laura Perin; Sargis Sedrakyan; Stefano Giuliani; Caterina Tiozzo; Jooeun Lee; Gianluca Turcatel; Stijn P De Langhe; Barbara Driscoll; Saverio Bellusci; Parviz Minoo; Anthony Atala; Roger Edward De Filippo; David Warburton Journal: Stem Cells Date: 2008-08-21 Impact factor: 6.277
Authors: Anna Milanesi; Jang-Won Lee; Zhenhua Li; Stefano Da Sacco; Valentina Villani; Vanessa Cervantes; Laura Perin; John S Yu Journal: PLoS One Date: 2012-08-07 Impact factor: 3.240
Authors: Vikash Chandra; G Swetha; Sudhakar Muthyala; Amit K Jaiswal; Jayesh R Bellare; Prabha D Nair; Ramesh R Bhonde Journal: PLoS One Date: 2011-06-07 Impact factor: 3.240
Authors: Chia-Wei Cheng; Valentina Villani; Roberta Buono; Min Wei; Sanjeev Kumar; Omer H Yilmaz; Pinchas Cohen; Julie B Sneddon; Laura Perin; Valter D Longo Journal: Cell Date: 2017-02-23 Impact factor: 41.582
Authors: Valentina Villani; Matthew E Thornton; Heather N Zook; Christiana J Crook; Brendan H Grubbs; Giuseppe Orlando; Roger De Filippo; Hsun Teresa Ku; Laura Perin Journal: Stem Cells Transl Med Date: 2019-10-21 Impact factor: 6.940