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Review
. 2014 Aug 22;345(6199):1247391.
doi: 10.1126/science.1247391.

Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease

Ira J Fox  1 , George Q Daley  2 , Steven A Goldman  3 , Johnny Huard  4 , Timothy J Kamp  5 , Massimo Trucco  6
Affiliations
Review

Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease

Ira J Fox et al. Science. .

Abstract

Pluripotent stem cells (PSCs) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically affect blood component and hematopoietic stem cell therapies and should facilitate treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types is needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful cell transplantation will require optimizing the best cell type and site for engraftment, overcoming limitations to cell migration and tissue integration, and occasionally needing to control immunologic reactivity, as well as a number of other challenges. Collaboration among scientists, clinicians, and industry is critical for generating new stem cell-based therapies.

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Figures

Figure 1
Figure 1
Comparison of intrahepatic engraftment of intact islets versus isolated beta cells following intraportal transplantation. A. Transplanted islet (in brown) within the capillary of the liver following intraportal transplantation. From (28) with permission. B iPS-derived beta cells (in brown) engraft as cells scattered throughout the liver parenchyma, from (150), with permission
Figure 1
Figure 1
Comparison of intrahepatic engraftment of intact islets versus isolated beta cells following intraportal transplantation. A. Transplanted islet (in brown) within the capillary of the liver following intraportal transplantation. From (28) with permission. B iPS-derived beta cells (in brown) engraft as cells scattered throughout the liver parenchyma, from (150), with permission
Figure 2
Figure 2
Illustration of traditional portal vein infusion of insulin producing cells for engraftment in the liver versus endoscopic placement of transplanted cells in the gastric sub-mucosal space.
Figure 3
Figure 3
Normal control liver (behind) and liver with advanced cirrhosis (in front), highlighting the structural differences that make liver failure from cirrhosis difficult to treat by intrahepatic cell therapy. Images courtesey of Dr. Rodney Markin, University of Nebraska Medical Center.
Figure 4
Figure 4
Schematic representation of how PSC-derived glial and neural cells populations might be employed to treat a vast array of neurologic and retinal diseases.
Figure 5
Figure 5
Importance of cell type for restoration of dystrophin expressing myofibers. Engraftment efficiency for muscle-derived stem cells (left) and myoblasts (right) following transplant.
Figure 6
Figure 6
Fibrin patch-based delivery of human PSC-derived ECs and SMCs. A) cardiac MRI from normal, MI, and cell-treatment groups at end systole (left) and end diastole (right); B) after infarction, the cell-treatment produced significantly smaller infarct size (delayed-enhancement MRI); C) and improved ejection fraction compared to MI alone. *P<0.05 vs MI alone. Modified from (147), with permission.
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