Abstract
Orthotopic liver transplantation (OLT) has been effective in managing end-stage liver disease since the advent of cyclosporine immunosuppression therapy in 1980. The major limitations of OLT are organ supply, monetary cost, and the burden of lifelong immunosuppression. Hepatocyte transplantation, as a substitute for OLT, has been an exciting topic of investigation for several decades. HT is potentially minimally invasive and can serve as a vehicle for delivery of personalized medicine through autologous cell transplant after modification ex vivo. However, 3 major hurdles have prevented large-scale clinical application: (1) availability of transplantable cells; (2) safe and efficient ex vivo gene therapy methods; and (3) engraftment and repopulation efficiency. This review will discuss new sources for transplantable liver cells obtained by lineage reprogramming, clinically acceptable methods of genetic manipulation, and the development of hepatic irradiation–based preparative regimens for enhancing engraftment and repopulation of transplanted hepatocytes. We will also review the results of the first 3 patients with genetic liver disorders who underwent preparative hepatic irradiation before hepatocyte transplantation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 922-934 |
| Number of pages | 13 |
| Journal | International Journal of Radiation Oncology Biology Physics |
| Volume | 103 |
| Issue number | 4 |
| DOIs | |
| State | Published - Mar 15 2019 |
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ASJC Scopus subject areas
- Radiation
- Oncology
- Radiology Nuclear Medicine and imaging
- Cancer Research
Cite this
Hepatocyte Transplantation : Quo Vadis? / Barahman, Mark; Asp, Patrik K.M.; Roy-Chowdhury, Namita; Kinkhabwala, Milan; Roy-Chowdhury, Jayanta; Kabarriti, Rafi; Guha, Chandan.
In: International Journal of Radiation Oncology Biology Physics, Vol. 103, No. 4, 15.03.2019, p. 922-934.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Hepatocyte Transplantation
T2 - Quo Vadis?
AU - Barahman, Mark
AU - Asp, Patrik K.M.
AU - Roy-Chowdhury, Namita
AU - Kinkhabwala, Milan
AU - Roy-Chowdhury, Jayanta
AU - Kabarriti, Rafi
AU - Guha, Chandan
PY - 2019/3/15
Y1 - 2019/3/15
N2 - Orthotopic liver transplantation (OLT) has been effective in managing end-stage liver disease since the advent of cyclosporine immunosuppression therapy in 1980. The major limitations of OLT are organ supply, monetary cost, and the burden of lifelong immunosuppression. Hepatocyte transplantation, as a substitute for OLT, has been an exciting topic of investigation for several decades. HT is potentially minimally invasive and can serve as a vehicle for delivery of personalized medicine through autologous cell transplant after modification ex vivo. However, 3 major hurdles have prevented large-scale clinical application: (1) availability of transplantable cells; (2) safe and efficient ex vivo gene therapy methods; and (3) engraftment and repopulation efficiency. This review will discuss new sources for transplantable liver cells obtained by lineage reprogramming, clinically acceptable methods of genetic manipulation, and the development of hepatic irradiation–based preparative regimens for enhancing engraftment and repopulation of transplanted hepatocytes. We will also review the results of the first 3 patients with genetic liver disorders who underwent preparative hepatic irradiation before hepatocyte transplantation.
AB - Orthotopic liver transplantation (OLT) has been effective in managing end-stage liver disease since the advent of cyclosporine immunosuppression therapy in 1980. The major limitations of OLT are organ supply, monetary cost, and the burden of lifelong immunosuppression. Hepatocyte transplantation, as a substitute for OLT, has been an exciting topic of investigation for several decades. HT is potentially minimally invasive and can serve as a vehicle for delivery of personalized medicine through autologous cell transplant after modification ex vivo. However, 3 major hurdles have prevented large-scale clinical application: (1) availability of transplantable cells; (2) safe and efficient ex vivo gene therapy methods; and (3) engraftment and repopulation efficiency. This review will discuss new sources for transplantable liver cells obtained by lineage reprogramming, clinically acceptable methods of genetic manipulation, and the development of hepatic irradiation–based preparative regimens for enhancing engraftment and repopulation of transplanted hepatocytes. We will also review the results of the first 3 patients with genetic liver disorders who underwent preparative hepatic irradiation before hepatocyte transplantation.
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U2 - 10.1016/j.ijrobp.2018.11.016
DO - 10.1016/j.ijrobp.2018.11.016
M3 - Review article
VL - 103
SP - 922
EP - 934
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
SN - 0360-3016
IS - 4
ER -