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Human peripheral blood CD34‐positive cells enhance therapeutic regeneration of chronically injured liver in nude rats
Author(s) -
Nakamura Toru,
Tsutsumi Victor,
Torimura Takuji,
Naitou Masako,
Iwamoto Hideki,
Masuda Hiroshi,
Hashimoto Osamu,
Koga Hironori,
Abe Mitsuhiko,
Ii Masaaki,
Kawamoto Atsuhiko,
Asahara Takayuki,
Ueno Takato,
Sata Michio
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22873
Subject(s) - cd34 , transplantation , peripheral blood mononuclear cell , pathology , chemistry , biology , andrology , medicine , stem cell , biochemistry , microbiology and biotechnology , in vitro
We investigated whether transplantation of purified human peripheral blood CD34 + cells could reduce established liver fibrosis and up‐regulate therapeutic regeneration. Human peripheral blood CD34 + cells were isolated from total mononuclear cells of healthy volunteers by magnetic cell sorting. Recipient nude rats were injected intraperitoneally with carbon tetrachloride (CCl 4 ) twice weekly for 3 weeks before single administration of CD34 + cells. CCl 4 was then re‐administered twice weekly for 3 more weeks, and the nude rats were sacrificed. Saline (control group), 1 × 10 5 (low‐dose group), 5 × 10 5 (middle‐dose group), or 2 × 10 6 (high‐dose group) CD34 + cells/kg body weight were intrasplenically transplanted after CCl 4 treatment for 3 weeks. Reverse transcriptase‐polymerase chain reaction analysis of the freshly isolated CD34 + cells revealed the expression of CD31, keratin19, α‐smooth muscle actin (α‐SMA), and epithelial growth factor, but not other liver related markers. The transplanted cells differentiated into vascular and sinusoidal endothelial cells, and vascular smooth muscle cells. CD34 + cell transplantation reduced liver fibrosis in a dose‐dependent fashion, with decreased collagen type‐I and α‐SMA‐positive cells after 6 weeks of CCl 4 treatment by Mallory's Azan and immunohistochemical staining. Gelatin zymography showed that the expression levels of active matrix metalloproteinase‐2 and ‐9 in CD34 + cell transplanted livers were significantly stronger than those in saline‐infused livers. In recipients of high‐doses of CD34 + cells, the number of PCNA‐positive hepatocyte increased 6 weeks after CCl 4 treatment compared with saline‐infused livers. We conclude that human peripheral blood CD34 + cell transplantation halts established liver fibrosis and promotes hepatic regeneration in CCl 4 ‐induced chronic liver injury. J. Cell. Physiol. 227: 1538–1552, 2012. © 2011 Wiley Periodicals, Inc.