Development of liver regenerative therapy using glycoside-modified bone marrow cells.
Several recent studies have reported that bone marrow cells (BMCs) have the ability to generate functional hepatocytes. However, the efficiency at which BMC transplantation generates functional hepatocytes is rather low. We assumed that if BMCs accumulated directly in liver, the functional BMC-derived hepatocytes should increase efficiently. We tried to increase the accumulation of BMCs directly in liver through the interaction between hepatic asialoglycoprotein receptor and desialylated BMCs. Desialylated BMCs were produced with treatment of neuraminidase. Desialylated BMCs that expressed green fluorescent protein (GFP) were injected into Long Evans Cinnamon (LEC) rats, a human Wilson's disease model, intravenously. At 3 and 5 months after transplantation, GFP-expressing hepatocyte nodules appeared in the liver of these BMC-transplanted LEC rats. These findings suggest that the functional BMC-derived hepatocytes can be generated by the direct accumulation of BMCs and that this strategy is new BMC therapy for liver regeneration.
Misawa
Ryosuke
R
Department of Organ Regeneration, Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
Ise
Hirohiko
H
Takahashi
Masafumi
M
Morimoto
Hajime
H
Kobayashi
Eiji
E
Miyagawa
Shin-ichi
S
Ikeda
Uichi
U
D000818:Animals; D030801:Animals, Genetically Modified; D037263:Asialoglycoprotein Receptor / Q000502:physiology; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005690:Galactose / Q000096:biosynthesis; D017930:Genes, Reporter; D006027:Glycosides / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D022781:Hepatocytes / Q000378:metabolism; D007150:Immunohistochemistry; D008107:Liver Diseases / Q000628:therapy*; D008115:Liver Regeneration / Q000235:genetics / Q000502:physiology*; D008297:Male; D009439:Neuraminidase / Q000494:pharmacology; D051381:Rats; D020332:Rats, Inbred LEC; D017208:Rats, Wistar
D037263:Asialoglycoprotein Receptor; D006027:Glycosides; D049452:Green Fluorescent Proteins; D009439:Neuraminidase; D005690:Galactose