scholarly journals Bone Marrow Stromal Cells: Characterization and Clinical Application

1999 ◽  
Vol 10 (2) ◽  
pp. 165-181 ◽  
Author(s):  
P.H. Krebsbach ◽  
S.A. Kuznetsov ◽  
P. Bianco ◽  
P. Gehron Robey
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Hematopoietic Cells ◽  
Marrow Stromal Cells ◽  
Proliferative Potential ◽  
Bone Marrow Stroma ◽  
Marrow Stroma

The bone marrow stroma consists of a heterogeneous population of cells that provide the structural and physiological support for hematopoietic cells. Additionally, the bone marrow stroma contains cells with a stem-cell-like character that allows them to differentiate into bone, cartilage, adipocytes, and hematopoietic supporting tissues. Several experimental approaches have been used to characterize the development and functional nature of these cells in vivo and their differentiating potential in vitro. In vivo, presumptive osteogenic precursors have been identified by morphologic and immunohistochemical methods. In culture, the stromal cells can be separated from hematopoietic cells by their differential adhesion to tissue culture plastic and their prolonged proliferative potential. In cultures generated from single-cell suspensions of marrow, bone marrow stromal cells grow in colonies, each derived from a single precursor cell termed the colony-forming unit-fibroblast. Culture methods have been developed to expand marrow stromal cells derived from human, mouse, and other species. Under appropriate conditions, these cells are capable of forming new bone after in vivo transplantation. Various methods of cultivation and transplantation conditions have been studied and found to have substantial influence on the transplantation outcome The finding that bone marrow stromal cells can be manipulated in vitro and subsequently form bone in vivo provides a powerful new model system for studying the basic biology of bone and for generating models for therapeutic strategies aimed at regenerating skeletal elements.

p38MAPK Inhibitor LSN2322600 Modulates the Bone Marrow Microenvironment and Inhibits Osteoclastogenesis in Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5042-5042
Author(s):  
Kenji Ishitsuka ◽  
Teru Hideshima ◽  
Paola Neri ◽  
Sonia Vallet ◽  
Norihiko Shiraishi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Mononuclear Cells ◽  
Severe Combined Immunodeficiency ◽  
Marrow Stromal Cells ◽  
Skeletal Complications

Abstract The interaction between multiple myeloma (MM) cells and the bone marrow (BM) microenvironment plays a crucial role not only in proliferation and survival of MM cells, but also in osteoclastogenesis. In this study, we examined diverse potential of novel p38MAPK inhibitor LSN2322600 (LSN) for MM therapy in vitro and in vivo. The cytotoxic activity of LSN against MM cell lines was modest; however, LSN significantly enhances the cytotoxicity of Bortezomib by down-regulating Bortezomib-induced heat shock protein (HSP) 27 phosphorylation. We next examined the effects of LSN on cytokine secretion in MM cells, bone marrow stromal cells and osteoclast precursor cells. LSN inhibited IL-6 secretion from long-term cultured-bone marrow stromal cells (LT-BMSCs) and bone marrow mononuclear cells (BMMNCs) from MM patients in remission. LSN also inhibited MIP-1 α secretion by fresh tumor cells, BMMNCs and CD14 positive cells. Since these cytokines mediate osteoclastogenesis, we further examined whether LSN could inhibit osteoclastogenesis. Importantly, LSN inhibited in vitro osteoclastogenesis induced by macrophage-colony stimulating factor (M-CSF) and soluble receptor activator of nuclear factor- κ B ligand (sRANKL), as well as osteoclastogenesis in the severe combined immunodeficiency (SCID)-Hu mouse model of human MM. These results suggest that LSN represents a promising novel targeted strategy to reduce skeletal complications as well as to sensitize or overcome resistance to Bortezomib.

scholarly journals Identification of a Hematopoietic Cell Population Emerging From Mouse Bone Marrow With Proliferative Potential In Vitro and Immunomodulatory Capacity

2021 ◽  
Vol 12 ◽  
Author(s):  
Catalina-Iolanda Marinescu ◽  
Mihai Bogdan Preda ◽  
Carmen Alexandra Neculachi ◽  
Evelyn Gabriela Rusu ◽  
Sinziana Popescu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Hematopoietic Cells ◽  
Tumor Rejection ◽  
Proliferative Potential ◽  
Mouse Bone Marrow ◽  
Positive Outcomes ◽  
Immunomodulatory Properties

There is continuing interest in therapeutic applications of bone marrow-derived mesenchymal stromal cells (MSC). Unlike human counterparts, mouse MSC are difficult to propagate in vitro due to their contamination with adherent hematopoietic cells that overgrow the cultures. Here we investigated the properties of these contaminating cells, referred to as bone marrow-derived proliferating hematopoietic cells (BM-PHC). The results showed that both BM-PHC and MSC had strong immunomodulatory properties on T cells in vitro, with PGE2 and NO involved in this mechanism. However, BM-PHC were stronger immunomodulators than MSC, with CCL-6 identified as putative molecule responsible for superior effects. In vivo studies showed that, in contrast to BM-PHC, MSC endorsed a more rapid xenograft tumor rejection, thus indicating a particular context in which only MSC therapy would produce positive outcomes. In conclusion, bone marrow contains two cell populations with immunomodulatory properties, which are valuable sources for therapeutic studies in specific disease-relevant contexts.

Abstract P120: Increased [ca 2+ ] e Enhances Adipocyte Development In Bone Marrow Stroma

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Ryota Hashimoto ◽  
Youichi Katoh ◽  
Seigo Itoh ◽  
Takafumi Iesaki ◽  
Hiroyuki Daida ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Bone Marrow Stroma ◽  
Age Related ◽  
Marrow Stroma ◽  
High Concentrations ◽  
Adipocyte Development ◽  
Oil Red O

Background: Bone marrow stroma contains adipocytes, osteoblasts, and lymphohematopoietic donor cells. With age, fatty marrow gradually predominates in bone marrow stroma and is a factor underlying age-related fracture and anemia. Thus, it is important to understand the mechanism of adipocyte development in bone marrow stroma. Bone marrow Ca 2+ levels can reach high concentrations of 8 to 40 mM, while circulating plasma Ca 2+ levels normally range from 2.3 to 2.6 mM. However, the effects of a high extracellular calcium concentration ([Ca 2+ ] e ) on adipocyte development in bone marrow stroma remain largely unknown. Methods and Results: We studied the effects of high [Ca 2+ ] e on adipocyte development in bone marrow stroma. First, we used the fura-2 method to examine whether a change in [Ca 2+ ] e alters [Ca 2+ ] i levels in bone marrow stromal cells. Changes of [Ca 2+ ] e from 1.8 mM to 5.4 mM and 10.8 mM significantly increased [Ca 2+ ] i by 1.1 and 1.3 times, respectively. Next, bone marrow stromal cells were cultured for 14 days in high [Ca 2+ ] e (5.4 mM and 10.8 mM) and normal [Ca 2+ ] e (1.8 mM) conditions. Adipocyte development was monitored by Oil Red O staining of cytoplasmic lipids and by the activity of glycerol-3-phosphate dehydrogenase (GPDH). In 5.4 mM and 10.8 mM [Ca 2+ ] e , Oil Red O-stained cells increased significantly by 1.4 and 2.3 times, respectively, and GPDH activity increased significantly by 1.7 and 2.3 times, respectively, compared with the respective values in 1.8 mM [Ca 2+ ] e . Conclusions: These results indicate that high [Ca 2+ ] e induces an increase of [Ca 2+ ] i , which enhances adipocyte development in bone marrow stroma. Further studies are required to determine the influx pathway of Ca 2+ , since prevention of Ca 2+ influx into bone marrow stromal cells might suppress development of fatty marrow and reduce age-related fracture and anemia.

scholarly journals Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Jack M. Milwid ◽  
Takaharu Ichimura ◽  
Matthew Li ◽  
Yunxin Jiao ◽  
Jungwoo Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Kidney Injury ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Kidney Injury ◽  
Standard Of Care ◽  
Marrow Stromal Cells ◽  
Secreted Factors

Acute kidney injury is a devastating syndrome that afflicts over 2,000,000 people in the US per year, with an associated mortality of greater than 70% in severe cases. Unfortunately, standard-of-care treatments are not sufficient for modifying the course of disease. Many groups have explored the use of bone marrow stromal cells (BMSCs) for the treatment of AKI because BMSCs have been shown to possess unique anti-inflammatory, cytoprotective, and regenerative propertiesin vitroandin vivo. It is yet unresolved whether the primary mechanisms controlling BMSC therapy in AKI depend on direct cell infusion, or whether BMSC-secreted factors alone are sufficient for mitigating the injury. Here we show that BMSC-secreted factors are capable of providing a survival benefit to rats subjected to cisplatin-induced AKI. We observed that when BMSC-conditioned medium (BMSC-CM) is administered intravenously, it prevents tubular apoptosis and necrosis and ameliorates AKI. In addition, we observed that BMSC-CM causes IL-10 upregulation in treated animals, which is important to animal survival and protection of the kidney. In all, these results demonstrate that BMSC-secreted factors are capable of providing support without cell transplantation, and the IL-10 increase seen in BMSC-CM-treated animals correlates with attenuation of severe AKI.

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