Transplantation of microcarrier-attached hepatocytes into 90% partially hepatectomized rats

Abstract

We previously reported a method of intraperitoneal transplantation of liver cells attached to collagen-coated microcarriers, which resulted in prolonged survival and function of the transplanted cells. In the present study, we evaluated the efficacy of liver cell transplantation in providing metabolic support during acute liver insufficiency induced by 90% partial hepatectomy in rats. Ninety per cent of the liver mass (all lobes except the caudate lobe) was resected, and the rats were provided with 5% dextrose orally ad libitum upon regaining consciousness. This regimen results in severe hypoglycemia and death within 48 hr. When microcarrier-attached liver cells were transplanted into syngeneic and allogeneic recipients 3 days prior to 90% partial hepatectomy, significantly higher blood glucose levels were observed (p less than 0.01), compared to the levels in control rats which received injections of microcarriers, liver cells or medium alone. There was a marked improvement in long-term survival (40% survived longer than 28 days; p less than 0.001) in rats transplanted with microcarriers-attached cells. None of the rats given injections of microcarriers, liver cells or medium alone survived beyond 5 days. When liver cells alone or attached to microcarriers were injected intraperitoneally immediately after 90% partial hepatectomy, all rats became hypoglycemic and died within 48 hr, suggesting that vascularization of the transplant is required for function of the transplanted hepatocytes. The results indicate that intraperitoneal transplantation of microcarrier-attached hepatocytes prior to 90% partial hepatectomy in rats provides acute metabolic support resulting in improved survival.

Adult human articular chondrocytes in a microcarrier‐based culture system: expansion and redifferentiation

“…For example, epidermal and dermal cell-seeded microcarriers enhanced skin healing 14,15 and hepatocyte-seeded microcarriers have been shown to restore liver function in rats. 16 Microcarrier-cultivated porcine chondrocytes implanted into full-thickness porcine cartilage defects outperformed chondrocytes propagated in monolayers. 17 However, the putative advantage of leaving these cells on microcarriers during differentiation remains to be confirmed.…”

Hepatocyte transplantation in rats with decompensated cirrhosis

“…7,8 Theoretically, hepatocyte transplantation would be less invasive and technically less demanding than whole organ transplantation and, if the procedure could be performed percutaneously, recipients would not require prolonged hospitalization. Isolated liver cells can be cryopreserved for emergency use [9][10][11][12] and potentially modified genetically before transplantation to abrogate rejection or enhance function.…”

Acute Liver Failure

“…[63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78] Some of these developments may also address the issue of difficulty in finding a donor liver and use of alternative/innovative forms of transplantation. Artificial hepatic support systems are cell-based extracorporeal system incorporating hepatocytes, which take up various excretory and synthetic hepatic functions until the liver regenerates.…”

“…Hepatocyte transplantation uses hepatocytes rather than the whole organ for transplantation. [69][70][71][72][73][74][75] The procedure would be ideal for transfer of genes to individuals with genetic diseases, such as familial hypercholesterolemia, Griggler-Najjar syndrome, etc. Extracorporeal liver (ECL) support system involves the diversion of patient's circulation through a liver outside the body.…”