Canine bone marrow cells differentiate into hepatocyte-like cells and placental hydrolysate is a potential inducer

ABSTRACT.Regenerative medicine using bone marrow cells is an attractive therapy for the cure of patients with severe liver disease. Here, we show the therapeutic potential of canine bone marrow stromal cells (BMSCs) in mouse models of CCl 4 -induced chronic liver dysfunction. We used two different models for xenotransplantation, nude mice and cyclosporine A (CSA) immunosuppressed mice. Serum parameters from a standard liver panel were not improved following transplantation. However, fibrotic liver lesions with severe inflammation were decreased in CCl 4 -treated CSA mice following BMSC transplantation. Effective migration of transplanted canine BMSCs was limited to persistently injured liver in CCl 4 -treated CSA mice, where they may be effective in resolving inflammatory fibrotic lesions. These results suggest that canine BMSCs are an effective cell source for liver regeneration.

Section: Discussionmentioning

confidence: 91%

“…Bone marrow stromal cells (BMSCs) are an attractive cell source for regenerative medicine, due to the ease of obtaining bone marrow stem cells compared to other tissue-specific stem cells. Many reports have shown the capacity of bone marrow stromal cells to differentiate into hepatocytes [2,[9][10][11]22].…”

mentioning

confidence: 99%

Therapeutic Potential of Canine Bone Marrow Stromal Cells (BMSCs) in the Carbon Tetrachloride (CCl4) Induced Chronic Liver Dysfunction Mouse Model

Haraguchi

Tani

Takagishi

et al. 2012

“…The staining reaction was stopped with addition of 1% bovine serum albumin, followed by washing with PBS. Labeling and viability were verified by cultivation in hepatocyte growth medium as previously described [15].…”

Section: Animalsmentioning

confidence: 99%

“…We previously demonstrated the capacity of canine BMCs (cBMCs) for differentiation into albumin-producing hepatocyte-like cells [15]. It has also been shown that bone marrow stromal cells (BMSCs), which are one of the components of BMCs, have various therapeutic potentials such as matrix metalloproteinase activity [7].…”

mentioning

confidence: 99%

Accumulation of Xenotransplanted Canine Bone Marrow Cells in NOD/SCID/γcnull Mice with Acute Hepatitis Induced by CCl4

Kato

Hisasue

Segawa

et al. 2013

Self Cite

ABSTRACT. Bone marrow cell infusion (BMI) has recently been suggested as an effective therapy for refractory liver disease; however, the efficiency of BMI using canine bone marrow cells (cBMCs) has not been reported. We evaluated the accumulation potential of cBMCs in a mouse model of acute liver failure. Acute hepatitis was induced by carbon tetrachloride (CCl 4 ) treatment in NOD/SCID/γ c null (NOG) mice and wild-type (WT) C57BL mice, and the characteristics of liver dysfunction and the degree of hepatic injury and regeneration were compared between the two mouse models. Next, female CCl 4 -treated NOG mice were xenotransplanted with male PKH26-labeled cBMCs, and the potential of cBMCs to accumulate in injured liver tissue compartments was examined. Fluorescence microscopy was performed to histologically detect the infused cBMCs, and DNA polymerase chain reaction was performed for detection of the male Y chromosome (SRY gene) in the recipient female NOG mice. The number of PKH26-positive cBMCs transplanted in the liver tissue gradually increased in the NOG mice. The infused cBMCs were located in the necrotic area of the liver at an early stage after transplantation, and most had accumulated a week after transplantation. However, the therapeutic efficacy of the xenotransplantation remained unclear, because no significant differences were observed concerning the extent liver injury and regeneration between the cBMC-transplanted and saline control mice. These results suggest that cBMCs will specifically accumulate in injured liver tissue and that BMC transplantation may have the potential to repair liver deficiency. KEY WORDS: canine bone marrow cell, carbon tetrachloride (CCl 4 ), cell therapy, liver regeneration, NOD/SCID/γ c null (NOG) mouse.

“…Recent clinical papers in human medicine present the effective therapeutic regime using autologous bone marrow stromal cells (BMSCs) for the patients with severe hepatic fibrosis [21]. Effect of the cell therapy has been explained by differentiation of the bone marrow cells into a variety of non-hematopoietic cell lineages [15] including hepatocytes [1,14,17,23]. Bone marrow cells are an attractive cell source for regenerative medicine compared to tissue-specific stem cells [7].…”

mentioning

confidence: 99%

Matrix Metalloproteinases (MMPs) Activity in Cultured Canine Bone Marrow Stromal Cells (BMSCs)

Haraguchi

Tani

Koga

et al. 2012

ABSTRACT. Autologous bone marrow stromal cells (BMSCs) infusion therapy improves the hepatic fibrosis. To investigate the mechanism of remission, we evaluated the matrix metalloproteinase (MMP)-2 and -9 activity in canine BMSCs and the effect of pro-inflammatory cytokines on their expression. The activity and the gene expression of MMPs were analyzed by gelatin zymography and quantitative RT-PCR, respectively. The specific gelatinase bands were indicative effect of MMP-2 and -9 in canine BMSCs. MMP-2 expression seemed to be increased by TNF-α and IL-1β while MMP-9 was enhanced by TNF-α and IL-6. These results suggested that remissive effect on liver fibrosis might be partly attributable to the MMP-2 and -9 activity in BMSCs under the inflammatory condition. KEY WORDS: bone marrow stromal cell (BMSC), canine, culture, inflammatory cytokines, matrix metalloproteinase (MMPs).