Cell-Based Therapy by Implanted Human Bone Marrow-Derived Mononuclear Cells Improved Bone Healing of Large Bone Defects in Rats

Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have been studied for their application to manage various neurological diseases, owing to their anti-inflammatory, immunomodulatory, paracrine, and antiapoptotic ability, as well as their homing capacity to specific regions of brain injury. Among mesenchymal stem cells, such as BM-MSCs, adipose-derived MSCs, and umbilical cord MSCs, BM-MSCs have many merits as cell therapeutic agents based on their widespread availability and relatively easy attainability and in vitro handling. For stem cell-based therapy with BM-MSCs, it is essential to perform ex vivo expansion as low numbers of MSCs are obtained in bone marrow aspirates. Depending on timing, before hBM-MSC transplantation into patients, after detaching them from the culture dish, cell viability, deformability, cell size, and membrane fluidity are decreased, whereas reactive oxygen species generation, lipid peroxidation, and cytosolic vacuoles are increased. Thus, the quality and freshness of hBM-MSCs decrease over time after detachment from the culture dish. Especially, for neurological disease cell therapy, the deformability of BM-MSCs is particularly important in the brain for the development of microvessels. As studies on the traditional characteristics of hBM-MSCs before transplantation into the brain are very limited, omics and machine learning approaches are needed to evaluate cell conditions with indepth and comprehensive analyses. Here, we provide an overview of hBM-MSCs, the application of these cells to various neurological diseases, and improvements in their quality and freshness based on integrated omics after detachment from the culture dish for successful cell therapy.

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Isolation Yield and Osteogenic Potential of Human Bone Marrow Stromal Cells are Maintained Irrespective of Age or Gender

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.361-363.1149 ◽

2007 ◽

Vol 361-363 ◽

pp. 1149-1152

Author(s):

Jeong Joon Yoo ◽

Jeon Hyun Bang ◽

Kyung Hoi Koo ◽

Kang Sup Yoon ◽

Hee Joong Kim

Keyword(s):

Bone Marrow ◽

Osteogenic Differentiation ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Mononuclear Cells ◽

Marrow Stromal Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Osteogenic Potential ◽

Donor Age

The relationships between donor age and gender and initial isolation yield and the osteogenic potentials of human bone marrow stromal cells (hBMSCs) have not been clearly elucidated. The authors investigated whether isolation yields and the osteogenic differentiation potentials of hBMSCs are indeed dependent on donor age or gender. Fresh bone marrow was aspirated from iliac crest of 72 donors (mean age 54.1 years; range, 23-84 years; 39 men and 33 women) undergoing total hip arthroplasty. Numbers of mononuclear cells, numbers of colony forming unit-fibroblasts (CFU-Fs) and alkaline phosphatase (ALP)-positive CFU-Fs, and numbers of BMSCs after isolation culture were not found to be significantly dependent on donor age or gender. Moreover, no significant age- or gender-related differences were observed in terms of the proliferation activities, ALP activities, and calcium contents of BMSCs during in vitro osteogenic differentiation. The data obtained from 72 human donors revealed no significant age- or genderrelated differences among hBMSCs in terms of isolation yields, proliferation activities, and osteogenic potentials.

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Arachidonic Acid and Freshly Isolated Human Bone Marrow Mononuclear Cells

Mediators of Inflammation ◽

10.1080/09629359990694 ◽

1999 ◽

Vol 8 (1) ◽

pp. 31-35 ◽

Cited By ~ 3

Author(s):

Y. Denizot ◽

V. Desplat ◽

C. Dulery ◽

F. Trimoreau ◽

V. Praloran

Keyword(s):

Bone Marrow ◽

Arachidonic Acid ◽

Fatty Acid ◽

Mononuclear Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Bone Marrow Mononuclear Cells ◽

Gm Csf ◽

Chromatography Analysis ◽

Bone Marrow Plasma

Arachidonic acid (AA), a fatty acid found in the human bone marrow plasma, is the precursor of eicosanoids that modulate bone marrow haematopoiesis. To further our understanding of the role of AA in the bone marrow physiology, we have assessed its incorporation in human bone marrow mononuclear cells. Gas chromatography analysis indicates the presence of AA in their fatty acid composition. In bone marrow mononuclear cells, [3H]-AA is incorporated into triglycerides and is later delivered into phospholipids, a result not observed with blood mononuclear cells. Prelabelling-chase experiments indicate a trafficking of labelled AA from phosphatidylcholine to phosphatidylethanolamine. Stimulation of prelabelled bone marrow mononuclear cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) results in the release of a part of the incorporated labelled AA. Finally, exogenous AA (up to 1 μM) has no significant effect on cell growth. In conclusion, human bone marrow mononuclear cells participate to the control of marrow AA concentrations by incorporating AA into phospholipids and triglycerides. In turn, bone marrow mononuclear cells can release AA in response to the potent haematopoietic growth factor GM-CSF.

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Differential effects of nitric oxide on erythroid and myeloid colony growth from CD34+ human bone marrow cells

Blood ◽

10.1182/blood.v87.3.977.bloodjournal873977 ◽

1996 ◽

Vol 87 (3) ◽

pp. 977-982 ◽

Cited By ~ 56

Author(s):

PJ Shami ◽

JB Weinberg

Keyword(s):

Bone Marrow ◽

Mononuclear Cells ◽

Bone Marrow Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Monocytic Differentiation ◽

Colony Forming Unit ◽

Normal Human ◽

Normal Human Bone Marrow ◽

Marrow Cells

Nitric oxide (NO) is a reactive molecule with numerous physiologic and pathophysiologic roles affecting the nervous, cardiovascular, and immune systems. In previous work, we have demonstrated that NO inhibits the growth and induces the monocytic differentiation of cells of the HL- 60 cell line. We have also demonstrated that NO inhibits the growth of acute nonlymphocytic leukemia cells freshly isolated from untreated patients and increases monocytic differentiation antigens in some. In the present work, we studied the effect of NO on the growth and differentiation of normal human bone marrow cells in vitro. Mononuclear cells isolated from human bone marrow were cultured in semisolid media and treated with the NO-donating agents sodium nitroprusside (SNP) or S- nitroso-acetyl penicillamine (SNAP) (0.25 to 1 mmol/L). Both agents decreased colony-forming unit-erythroid (CFU-E) and colony-forming unit- granulocyte macrophage (CFU-GM) formation by 34% to 100%. When CD34+ cells were examined, we noted that these cells responded to SNP and SNAP differently than did the mononuclear cells. At a concentration range of 0.25 to 1 mmol/L, SNP inhibited the growth of CFU-E by 30% to 75%. However, at the same concentration range, SNP increased the number of CFU-GM by up to 94%. At concentrations of 0.25 to 1 mmol/L, SNAP inhibited the growth of CFU-E by 33% to 100%. At a concentration of 0.25 mmol/L, SNAP did not affect CFU-GM. At higher concentrations, SNAP inhibited the growth of CFU-GM. Although SNP increased intracellular levels of cGMP in bone marrow cells, increasing cGMP in cells by addition of 8-Br-cGMP (a membrane permeable cGMP analogue) did not reproduce the observed NO effects on bone marrow colonies. These results demonstrate that NO can influence the growth and differentiation of normal human bone marrow cells. NO (generated in the bone marrow microenvironment) may play an important role modulating the growth and differentiation of bone marrow cells in vivo.

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