Change in hematopoietic function of lethal dose irradiated mice models following skeletal muscle satellite cells transplantation

Tao WANG; Xiaoling WANG; Shuwu ZHAO; Junmin TANG

ABSTRACT

BACKGROUND:

Skeletal muscle satellite cells are muscle-derived stem cells with proliferation and differentiation potential. Recently, foreign researches have reported that skeletal muscle satellite cells can be activated by some definite microenvironmental factors and differentiate into hematopoietic stem cells and thereby they will have the potential of hematopoietic reconstruction.

OBJECTIVE:

To initially validate the potential of adult muscle-derived stem cells- skeletal muscle satellite cells differentiating into hematopoietic stem cells.

DESIGN:

Validation animal experiment.

SETTING:

Department of Histology and Embryology, College of Basic Medical Science, Tianjin University of Traditional Chinese Medicine.MATERIALS Sixty-five male Kunming adult mice, weighing 25-28 g, were involved in this study. Five Kunming neonate rats, aged 5 days, were provided by the Laboratory Animal Center, Department of Medicine, Peking University.

METHODS:

This experiment was carried out in the Laboratory for Cell Culture, Department of Human Anatomy and Histo-embryology, School of Basic Medical Sciences, Peking University Health Science Center between August 2001 and August 2003. Skeletal muscle satellite cells of 5 neonate rats were isolated by collagenase and trypsin digestion. Bone marrow mononuclear cells of 5 adult Kunming mice were isolated. Sixty adult female mice were used as recipients, irradiated with 60Coγ 8.0 Gy and then randomized into 4 groups control group, in which, the mice were untouched; culture fluid infusion group, in which, the mice were injected with DMEM/F-12 medium through caudal vein; satellite cell infusion group, in which, the mice were injected with 0.3 mL satellite cell suspension through caudal vein (cell concentration 1×109 L-1); bone marrow-derived cell infusion group, in which, the mice were injected with 0.3 mL bone marrow-derived cell suspension (cell concentration 1×109 L-1) through caudal vein.MAIN OUTCOME

MEASURES:

①The survival rate of 14-day-old mice in each group. ②The surviving recipient mice were euthanized 14 days after irradiation, and tubercles on the surface of spleen were counted by naked observation; Bone marrow mononuclear cell smear was stained by Wright-Gimesa.

RESULTS:

① Determination of colony forming unit-spleen (CFU-S) No significant difference in the number of spleen tubercles of mice existed between satellite cell infusion group and bone marrow-derived cell infusion group 14 days after irradiation (P＞0.05). ②Histological identification of bone marrow-derived mononuclear cells Many hematopoietic cells appeared at the early stage in the bone marrow-derived mononuclear cell smears between satellite cell infusion group and bone marrow-derived cell infusion group. Their morphology meets the biological characteristics of hematopoietic cells at the early stage. ③ The survival condition of irradiated mice All the mice in the control group and culture fluid infusion group died 9 to 13 days after irradiation. In contrast, 8 mice from the satellite cell infusion group and 13 the bone marrow-derived cell infusion group survived 14 days after irradiation.

CONCLUSION:

Skeletal muscle satellite cells have the function of differentiating into hematopoietic stem cells.