• Journal of Veterinary Science
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• v.22 no.6
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• pp.74.1-74.13
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• 2021

Tissue engineering has been extensively investigated and proffered to be a potential platform for novel tissue regeneration. The utilization of mesenchymal stem cells (MSCs) from various sources has been widely explored and compared. In this regard, MSCs derived from bone marrow have been proposed and described as a promising cell resource due to their high yield of isolated cells with colony-forming potential, self-renewal capacity, MSC surface marker expression, and multi-lineage differentiation capacities in vitro. However, there is evidence for bone marrow MSCs (BM-MSCs) both in vitro and in vivo from different species presenting identical and distinct potential stemness characteristics. In this review, the fundamental knowledge of the growth kinetics and stemness properties of BM-MSCs in different animal species and humans are compared and summarized. Finally, to provide a full perspective, this review will procure results of current information studies focusing on the use of BM-MSCs in clinical practice.

• BMB Reports
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• v.53 no.12
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• pp.646-651
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• 2020

Bone resorption is linked to bone formation via temporal and spatial coupling within the remodeling cycle. Several lines of evidence point to the critical role of coupling factors derived from pre-osteoclasts (POCs) during the regulation of bone marrow-derived mesenchymal stem cells (BMMSCs). However, the role of glial cell-derived neurotrophic factor (GDNF) in BMMSCs is not completely understood. Herein, we demonstrate the role of POC-derived GDNF in regulating the migration and osteogenic differentiation of BMMSCs. RNA sequencing revealed GDNF upregulation in POCs compared with monocytes/macrophages. Specifically, BMMSC migration was inhibited by a neutralizing antibody against GDNF in pre-osteoclast-conditioned medium (POC-CM), whereas treatment with a recombinant GDNF enhanced migration and osteogenic differentiation. In addition, POC-CM derived from GDNF knock-downed bone marrow macrophages suppressed BMMSC migration and osteogenic differentiation. SPP86, a small molecule inhibitor, inhibits BMMSC migration and osteogenic differentiation by targeting the receptor tyrosine kinase RET, which is recruited by GDNF into the GFRα1 complex. Overall, this study highlights the role of POC-derived GDNF in BMMSC migration and osteogenic differentiation, suggesting that GDNF regulates bone metabolism.

• Journal of Periodontal and Implant Science
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• v.41 no.4
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• pp.192-200
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• 2011

Purpose: The aim of this study is to compare the gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow for characterization of dental stem cells. Methods: We employed GeneChip analysis to the expression levels of approximately 32,321 kinds of transcripts in 5 samples of bone-marrow-derived mesenchymal stem cells (BMSCs) (n=1), periodontal ligament stem cells (PDLSCs) (n=2), and dental pulp stem cells (DPSCs) (n=2). Each cell was sorted by a FACS Vantage Sorter using immunocytochemical staining of the early mesenchymal stem cell surface marker STRO-1 before the microarray analysis. Results: We identified 379 up-regulated and 133 down-regulated transcripts in BMSCs, 68 up-regulated and 64 down-regulated transcripts in PDLSCs, and 218 up-regulated and 231 down-regulated transcripts in DPSCs. In addition, anatomical structure development and anatomical structure morphogenesis gene ontology (GO) terms were over-represented in all three different mesenchymal stem cells and GO terms related to blood vessels, and neurons were over-represented only in DPSCs. Conclusions: This study demonstrated the genome-wide gene expression patterns of STRO-$1^+$ mesenchymal stem cells derived from dental tissues and bone marrow. The differences among the expression profiles of BMSCs, PDLSCs, and DPSCs were shown, and 999 candidate genes were found to be definitely up- or down-regulated. In addition, GOstat analyses of regulated gene products provided over-represented GO classes. These data provide a first step for discovering molecules key to the characteristics of dental stem cells.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.30 no.2
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• pp.133-141
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• 2008

Stem cells have self-renewal capacity, long-term viability, and multiline age potential. Adult bone marrow contains mesenchymal stem cells. Bone marrow-derived mesenchymal stem cells (BMSCs) are progenitors of skeletal tissue components and can differentiate into adipocytes, chondrocytes, osteoblasts, and myoblasts in vitro and undergo differentiation in vivo. However, the clinical use of BMSCs has presented problems, including pain, morbidity, and low cell number upon harvest. Recent studies have identified a putative stem cell population within the adipose tissue. Human adipose tissue contains pluripotent stem cells simillar to bone marrow-derived stem cells that can differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages. Human adipose tissue-derived stem cells (ATSCs) could be proposed as an alternative source of adult bone marrow stem cells, and could be obtained in large quantities, under local anesthesia, with minimal discomfort. Human adipose tissue obtained by liposuction was processed to obtain ATSCs. In this study, we compared the osteogenic differentiation of ATSCs in a specific osteogenic induction medium with that in a non-osteogenic medium. ATSCs were incubated in an osteogenic medium for 28 days to induce osteogenesis respectively. Osteogenic differentiation was assessed by von Kossa and alkaline phosphatase staining. Expression of osteocyte specific bone sialoprotein, osteocalcin, collagen type I and alkaline phosphatase, bone morphogenic protein 2, bone morphogenic protein 6 was confirmed by RT-PCR. ATSCs incubated in the osteogenic medium were stained positively for von Kossa and alkaline phosphatase staining. Expression of osteocyte specific genes was also detected. Since this cell population can be easily identified through fluorescence microscopy, it may be an ideal source of ATSCs for further experiments on stem cell biology and tissue engineering. The present results show that ADSCs have an ability to differentiate into osteoblasts. In the present study, we extend this approach to characterize adipose tissue-derived stem cells.

• IMMUNE NETWORK
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• v.1 no.3
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• pp.179-186
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• 2001

Bone marrow stroma is a complex tissue encompassing a number of cell types and supports hematopiesis, differentiation of erythreid, nyel and lymphoid lineages, and also maintains undifferentiated hematopoietic stem cells. Marrow-derived stem cells were composed of two populations, namely, hematopoietic stem cells that can differentiate into blood elements and mesenchymal stem cells that can give rise to connective tissues such as bone, cartilage, muscle, tendon, adipose and stroma. Differentiation requires environmental factors and unique intracellular signaling. For example, $TGF-{\beta}$ or BMP2 induces osteoblastic differentiation of mesenchymal stem are very exciting. However, the intrinsic controls involved in differentiation of stem cells are yet to be understood properly in order to exploit the same. This review presents an overview of the recent developments made in mesenchymal stem cell research with respect to osteogenesis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.6
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• pp.397-402
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• 2009

The purpose of this study is to investigate the effects of alendronate and pamidronate on proliferation and the alkaline phosphatase activity of human bone marrow derived mesenchymal stem cells and to relate the results with bisphosphonate related osteonecrosis of the jaw(BRONJ). With the consent of patients with no systemic disease and undergoing iliac bone graft, cancellous bone was collected to obtain human bone marrow derived mesenchymal stem cells through cell culture. 96 well plate were prepared with a concentration of $10^4$cell/ well. Alendronate and pamidronate were added to each well with the concentration of $10^{-6}M$, $10^{-8}M$ and $10^{-10}M$, respectively. Then proliferation capacity of each well was evaluated with the cell counting kit. 24 well plates were prepared with a concentration of $10^5$cell/ml/well and with the bone supplement, alendronate and pamidronate were added with the concentration of $10^{-6}M$, $10^{-8}M$ and $10^{-10}M$, respectively on each plate. The plates were cultured for either 24 or 72 hours. Then the cells were sonicated to measure the alkaline phosphatase activity and protein assay was done to standardize the data for analysis. As the concentration of alendronate or pamidronate added to the culture increased, the proliferation capacity of the cells decreased. However, no statistical significance was found between the group with $10^{-10}M$ of bisphophonate and the control group. Pamidronate was not capable of increasing the alkaline phosphatase activity in all trials. However, alkaline phosphatase activity increased with 24 hours of $10^{-8}M$ of alendronate treatment and with 48 hours of $10^{-10}M$ of alendronate treatment. Cell toxicity increased as the bisphosphonate concentration increased. This seems to be associated with the long half life of bisphosphonate, resulting in high concentration of bisphosphonate in the jaw and thus displaying delayed healing after surgical procedures. Alendronate has shown to increase the alkaline phophatase activity of human bone marrow derived mesenchymal stem cells. However, this data is insufficient to conclude that alendronate facilitates the differentiation of human bone marrow derived mesenchymal stem cells. Further studies on DNA level and animal studies are required to support these results.

• Journal of Embryo Transfer
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• v.23 no.2
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• pp.127-131
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• 2008

Bone marrow (BM) cell harvesting is a crucial element in the isolation of mesenchymal stem cells (MSCs). A simple method for harvesting cat BM cells is described. The results show that a large number of BM cells can rapidly be harvested from the cat by this simple procedure. MSCs prepared by density-gradient method were spindle-shaped morphology with bipolar or polygonal cell bodies and strongly positive for CD9 and CD44 and negative for CD18 and CD45-like. They were capable of differentiation to adipocytic and osteocytic phenotypes when exposed to appropriate induction media. The advantages of this method are its rapidity, simplicity, low invasiveness, and low donor attrition and good outcome.

• Clinics in Shoulder and Elbow
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• v.15 no.2
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• pp.65-72
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• 2012

Purpose: To evaluate the differentiation potential of stem cells and their immunophenotype from 3 different sources. Methods: Our study involved three stem cell sources-subacromial bursal tissue, bone marrow, and umbilical cord blood. We obtained the subacromial bursal tissue and bone marrow from the patients undergoing shoulder surgery. After collecting the sample, we applied specific induction media for neurogenic, adipogenic and osteogenic differentiation. Also, flow-cytometry analysis was done to reveal the cell surface antigens. Results: We obtained 100% (8 cases) neural and adipogenic differentiation, but 62.5% (5 of 8 cases) osseous differentiation among the subacromial bursal tissue group. Bone marrow derived cells showed 100% neural (6 cases) and adipogenic (5 cases) differentiation, but 80% (4 of 5 cases) osseous differentiation. Umbilical cord blood derived cells revealed 97% (65 of 67 cases) neural, 53.7% (29 of 54 cases) adipogenic and 68.4% (39 of 57 cases) osseous differentiation. Immunophenotype analysis revealed that surface markers of bone marrow, subacromial bursal cell and umbilical cord blood derived mesenchymal stem cells are different from each other. Conclusions: Mesenchymal stem cells are potential agents in regenerative medicine and are characterized by expression of surface markers and by their differentiation potential. Our study with stem cells from subacromial bursal tissue, bone marrow and umbilical cord discovered that each stem cell has unique differentiation potential and function based on its origin. Various stem cells show multi-lineage differentiations in vitro which can be correlated to in vivo conditions.

• Molecules and Cells
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• v.37 no.9
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• pp.650-655
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• 2014

Mesenchymal stem cells (MSCs) can differentiate into neural cells to treat nervous system diseases. Magnetic resonance is an ideal means for cell tracking through labeling cells with superparamagnetic iron oxide (SPIO). However, no studies have described the neural differentiation ability of SPIO-labeled MSCs, which is the foundation for cell therapy and cell tracking in vivo. Our results showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) labeled in vitro with SPIO can be induced into neural-like cells without affecting the viability and labeling efficiency. The cellular uptake of SPIO was maintained after labeled BM-MSCs differentiated into neural-like cells, which were the basis for transplanted cells that can be dynamically and non-invasively tracked in vivo by MRI. Moreover, the SPIO-labeled induced neural-like cells showed neural cell morphology and expressed related markers such as NSE, MAP-2. Furthermore, whole-cell patch clamp recording demonstrated that these neural-like cells exhibited electrophysiological properties of neurons. More importantly, there was no significant difference in the cellular viability and $[Ca^{2+}]_i$ between the induced labeled and unlabeled neural-like cells. In this study, we show for the first time that SPIO-labeled MSCs retained their differentiation capacity and could differentiate into neural-like cells with high cell viability and a good cellular state in vitro.

• Molecules and Cells
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• v.38 no.3
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• pp.267-272
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• 2015

Nacre seashell is a natural osteoinductive biomaterial with strong effects on osteoprogenitors, osteoblasts, and osteoclasts during bone tissue formation and morphogenesis. Although nacre has shown, in one study, to induce bridging of new bone across large non-union bone defects in 8 individual human patients, there have been no succeeding human surgical studies to confirm this outstanding potency. But the molecular mechanisms associated with nacre osteoinduction and the influence on bone marrow-derived mesenchymal stem cells (BMSC's), skeletal stem cells or bone marrow stromal cells remain elusive. In this study we highlight the phenotypic and biochemical effects of Pinctada maxima nacre chips and the global nacre soluble protein matrix (SPM) on primary human bone marrow-derived stromal cells (hBMSCs) in vitro. In static co-culture with nacre chips, the hBMSCs secreted Alkaline phosphatase (ALP) at levels that exceeded bone morphogenetic protein (rhBMP-2) treatment. Concentrated preparation of SPM applied to Stro-1 selected hBMSC's led to rapid ALP secretions, at concentrations exceeding the untreated controls even in osteogenic conditions. Within 21 days the same population of Stro-1 selected hBMSCs proliferated and secreted collagens I-IV, indicating the premature onset of an osteoblast phenotype. The same SPM was found to promote unselected hBMSC differentiation with osteocalcin detected at 7 days, and proliferation increased at 7 days in a dose-dependent manner. In conclusion, nacre particles and nacre SPM induced the early stages of human bone cell differentiation, indicating that they may be promising soluble factors with osteoinductive capacity in primary human bone cell progenitors such as, hBMSC's.