TY - JOUR
T1 - Enhanced In Vivo Vascularization of 3D-Printed Cell Encapsulation Device Using Platelet-Rich Plasma and Mesenchymal Stem Cells
AU - Paez-Mayorga, Jesus
AU - Capuani, Simone
AU - Farina, Marco
AU - Lotito, Maria Luisa
AU - Niles, Jean A.
AU - Salazar, Hector F.
AU - Rhudy, Jessica
AU - Esnaola, Lucas
AU - Chua, Corrine Ying Xuan
AU - Taraballi, Francesca
AU - Corradetti, Bruna
AU - Shelton, Kathryn A.
AU - Nehete, Pramod N.
AU - Nichols, Joan E.
AU - Grattoni, Alessandro
N1 - Publisher Copyright:
© 2020 Wiley-VCH GmbH
PY - 2020/10/1
Y1 - 2020/10/1
N2 - The current standard for cell encapsulation platforms is enveloping cells in semipermeable membranes that physically isolate transplanted cells from the host while allowing for oxygen and nutrient diffusion. However, long-term viability and function of encapsulated cells are compromised by insufficient oxygen and nutrient supply to the graft. To address this need, a strategy to achieve enhanced vascularization of a 3D-printed, polymeric cell encapsulation platform using platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) is investigated. The study is conducted in rats and, for clinical translation relevance, in nonhuman primates (NHP). Devices filled with PRP, MSCs, or vehicle hydrogel are subcutaneously implanted in rats and NHP and the amount and maturity of penetrating blood vessels assessed via histopathological analysis. In rats, MSCs drive the strongest angiogenic response at early time points, with the highest vessel density and endothelial nitric oxide synthase (eNOS) expression. In NHP, PRP and MSCs result in similar vessel densities but incorporation of PRP ensues higher levels of eNOS expression. Overall, enrichment with PRP and MSCs yields extensive, mature vascularization of subcutaneous cell encapsulation devices. It is postulated that the individual properties of PRP and MSCs can be leveraged in a synergistic approach for maximal vascularization of cell encapsulation platforms.
AB - The current standard for cell encapsulation platforms is enveloping cells in semipermeable membranes that physically isolate transplanted cells from the host while allowing for oxygen and nutrient diffusion. However, long-term viability and function of encapsulated cells are compromised by insufficient oxygen and nutrient supply to the graft. To address this need, a strategy to achieve enhanced vascularization of a 3D-printed, polymeric cell encapsulation platform using platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) is investigated. The study is conducted in rats and, for clinical translation relevance, in nonhuman primates (NHP). Devices filled with PRP, MSCs, or vehicle hydrogel are subcutaneously implanted in rats and NHP and the amount and maturity of penetrating blood vessels assessed via histopathological analysis. In rats, MSCs drive the strongest angiogenic response at early time points, with the highest vessel density and endothelial nitric oxide synthase (eNOS) expression. In NHP, PRP and MSCs result in similar vessel densities but incorporation of PRP ensues higher levels of eNOS expression. Overall, enrichment with PRP and MSCs yields extensive, mature vascularization of subcutaneous cell encapsulation devices. It is postulated that the individual properties of PRP and MSCs can be leveraged in a synergistic approach for maximal vascularization of cell encapsulation platforms.
KW - cell encapsulation
KW - cell transplantation
KW - mesenchymal stem cells
KW - subcutaneous implants
KW - vascularization
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U2 - 10.1002/adhm.202000670
DO - 10.1002/adhm.202000670
M3 - Article
C2 - 32864893
AN - SCOPUS:85089961518
SN - 2192-2640
VL - 9
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 19
M1 - 2000670
ER -