Cell-delivery therapeutics for liver regeneration.
For acute, chronic, or hereditary diseases of the liver, cell transplantation therapies can stimulate liver regeneration or serve as a bridge until liver transplantation can be performed. Recently, fetal hepatocytes, stem cells, liver progenitor cells, or other primitive and proliferative cell types have been employed for cell transplantation therapies, in an effort to improve the survival, proliferation, and engraftment of the transplanted cells. Reviewing earlier studies, which achieved success by transplanting mature hepatocytes, we propose that there is a switch-like regulation of liver regeneration that changes state according to a stimulus threshold of extracellular influences such as cytokines, matrices and neighboring cells. Important determinants of a successful clinical outcome include sufficient quantities and functional levels of the transplanted cells (even for short periods to alter the environment), rather than just engraftment levels or survival durations of the exogenously transplanted cells. The relative importance of these determining factors will impact future choices of cell sources, delivery vehicles, and sites of cell transplantation to stimulate liver regeneration for patients with severe liver diseases.
Zhang
Wenxia
W
Department of Physiology, National University of Singapore, Singapore.
Tucker-Kellogg
Lisa
L
Narmada
B C
BC
Venkatraman
Lakshmi
L
Chang
Shi
S
Lu
Yin
Y
Tan
Nancy
N
White
Jacob K
JK
Jia
Ruirui
R
Bhowmick
Sourav Saha
SS
Shen
Shali
S
Dewey
C Forbes
CF
Yu
Hanry
H
D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods*; D022781:Hepatocytes / Q000637:transplantation; D006801:Humans; D008107:Liver Diseases / Q000473:pathology / Q000601:surgery*; D008115:Liver Regeneration; D012720:Severity of Illness Index; D054457:Tissue Scaffolds; D016896:Treatment Outcome