VENTRICULAR ARRHYTHMIAS FOLLOWING INTRAMYOCARDIAL INJECTIONS OF BONE MARROW STEM CELLS: AN ANIMAL MODEL

Cancer cachexia is a multifactorial systemic inflammation disease caused by complex interactions between the tumor and host tissues via soluble factors. However, whether cancer cachexia affects the bone marrow, in particular the hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), remains unclear. Here, we investigated the bone marrow and bone in a cancer cachexia animal model generated by transplanting Lewis lung carcinoma cells. The number of bone marrow mononuclear cells (BM-MNCs) started to significantly decrease in the cancer cachectic animal model prior to the discernable loss of muscle and fat. This decrease in BM-MNCs was associated with myeloid skewing in the circulation and the expansion of hematopoietic progenitors in the bone marrow. Bone loss occurred in the cancer cachexia animal model and accompanied the decrease in the bone marrow MSCs that play important roles in both supporting HSCs and maintaining bone homeostasis. Glucocorticoid signaling mediated the decrease in bone marrow MSCs in the cancer cachectic environment. The cancer cachexia environment also skewed the differentiation of the bone marrow MSCs toward adipogenic fate via JAK/STAT as well as glucocorticoid signaling. Our results suggest that the bone loss induced in cancer cachexia is associated with the depletion and the impaired differentiation capacity of the bone marrow MSCs.

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Investigating the Possibility of Intervertebral Disc Regeneration Induced by Granulocyte Colony Stimulating Factor-Stimulated Stem Cells in Rats

Advances in Orthopedics ◽

10.4061/2011/602089 ◽

2011 ◽

Vol 2011 ◽

pp. 1-5 ◽

Cited By ~ 10

Author(s):

Wen-Ching Tzaan ◽

Hsien-Chih Chen

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Intervertebral Disc ◽

Bone Marrow Stem Cells ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Hematopoietic Stem ◽

Disc Regeneration ◽

Intervertebral Disc Regeneration ◽

Stimulating Factor

Intervertebral disc (IVD) degeneration is a multifactorial process that is influenced by contributions from genetic predisposition, the aging phenomenon, lifestyle conditions, biomechanical loading and activities, and other health factors (such as diabetes). Attempts to decelerate disc degeneration using various techniques have been reported. However, to date, there has been no proven technique effective for broad clinical application. Granulocyte colony-stimulating factor (GCSF) is a growth factor cytokine that has been shown to enhance the availability of circulating hematopoietic stem cells to the brain and heart as well as their capacity for mobilization of mesenchymal bone marrow stem cells. GCSF also exerts significant increases in circulating neutrophils as well as potent anti-inflammatory effects. In our study, we hypothesize that GCSF can induce bone marrow stem cells differentiation and mobilization to regenerate the degenerated IVD. We found that GCSF had no contribution in disc regeneration or maintenance; however, there were cell proliferation within end plates. The effects of GCSF treatment on end plates might deserve further investigation.

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