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Therapeutic potential of mesenchymal stromal cells for acute respiratory distress syndrome.

Based on preclinical data, cell-based therapy with bone marrow-derived mesenchymal stem (stromal) cells (MSCs) is a potentially attractive new therapeutic option for treating patients with the acute respiratory distress syndrome. Small and large animal models of acute lung injury from endotoxin, live bacteria, and sepsis have shown that MSCs can decrease lung injury and increase survival. The mechanisms for benefit are mediated in part by paracrine release of several antiinflammatory cytokines, keratinocyte growth factor, angiopoietin-1, as well as the release of antimicrobial peptides. There

Propranolol and Mesenchymal Stromal Cells Combine to Treat Traumatic Brain Injury.

UNLABELLED: More than 6.5 million patients are burdened by the physical, cognitive, and psychosocial deficits associated with traumatic brain injury (TBI) in the U.S. Despite extensive efforts to develop neuroprotective therapies for this devastating disorder, there have been no successful outcomes in human clinical trials to date. Retrospective studies have shown that β-adrenergic receptor blockers, specifically propranolol, significantly decrease mortality of TBI through mechanisms not yet fully elucidated but are thought to counterbalance a hyperadrenergic state resulting from a TBI. Conver

Dissecting the role of bone marrow stromal cells on bone metastases.

Tumor-induced bone disease is a dynamic process that involves interactions with many cell types. Once metastatic cancer cells reach the bone, they are in contact with many different cell types that are present in the cell-rich bone marrow. These cells include the immune cells, myeloid cells, fibroblasts, osteoblasts, osteoclasts, and mesenchymal stem cells. Each of these cell populations can influence the behavior or gene expression of both the tumor cells and the bone microenvironment. Additionally, the tumor itself can alter the behavior of these bone marrow cells which further alters both t

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… Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Research. 2002;62(6):1832–1837. 48. Sun X, Cheng G, Hao M, et al. CXCL12 / CXCR4 / CXCR7 chemokine axis and cancer progression. … Stromal cells in tumor microenvironment and breast cancer. Cancer and Metastasis Reviews. 2013;32(1-2):303–315. doi: 10.1007/s10555-012-9415-3. 118. Tchou J, Conejo-Garcia J. …

Dysregulated cell mechanical properties of endometrial stromal cells from endometriosis patients.

Endometriosis, diagnosed with ectopically implanted endometrial stromal cells (ESC) and epithelial cells to a location outside the uterine cavity, seriously threaten the quality of life and reproductive ability of women, yet the mechanisms and the pathophysiology of the disease remain unclear. Specially, the functional changes of ESC during endometriosis progression need in-depth investigation. In this study, we characterized mechanical properties of normal ESC (NESC) from healthy women and eutopic ESC (EuESC) and ectopic ESC (EcESC) from endometriosis patients. We found the collagen lattice c…

[Autologous fat grafts and supportive enrichment with adipose tissue stromal cells].

Liposuction is a most common surgical procedure in aesthetic surgery that aims at the local fat reduction. The obtained adipose tissue is cu … tter is not attributed to the mature adipocytes, but rather to the undifferentiated adipose derived stromal cells (ASC). Thus enrichment of the fat graft with autologous ASC, known as cell-assisted lipotransfer (CAL) may lead to further optimisation of lipofilling concerning fat graft survival. Still aiming to establish the application of autologous fat grafts …

Protein profiling of anastomosed facial nerve treated with mesenchymal stromal cells.

BACKGROUND AIMS: The types of proteins released from mesenchymal stromal cells (MSC) are still unclear. Our aim was to compare apoptosis scores and the expression of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), neural cell adhesion molecule (NCAM)-1,matrix metalloproteinase (MMP)-1A, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-1/MMP-1A ratio, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), neurotrophin (NT)-3, NT-4, glial cell-derived neurotropic factor (GDNF), leukemia inhibitory factor (LIF), basic fibrobl…

IL-7-producing stromal cells are critical for lymph node remodeling.

Nonhematopoietic stromal cells of secondary lymphoid organs form important scaffold and fluid transport structures, such as lymph node (LN) trabeculae, lymph vessels, and conduits. Furthermore, through the production of chemokines and cytokines, these cells generate a particular microenvironment that determines lymphocyte positioning and supports lymphocyte homeostasis. IL-7 is an important stromal cell-derived cytokine that has been considered to be derived mainly from T-cell zone fibroblastic reticular cells. We show here that lymphatic endothelial cells (LECs) are a prominent source of IL-7…

[Mesenchymal stromal cells transplantation in acute and chronic pancreatitis in rats].

Before using MSC transplantation in the clinic to conduct preclinical studies MSCs to animals with acute and chronic pancreatitis. Work out the timing and dose of MSCs. The rationale of MSCs transplantation for the regeneration of damaged pancreatic tissue. The essence of the experiments is to establish the existence of common pathogenetic mechanisms for the development of pathological processes and sanogenesis toxic damage of pancreatic tissue. The study was work out in the rat model of acute and chronic pancreatitis, to explore beneficial and adverse effects of allogeneic stem cells for rege

Cellular and molecular phenotypes of proliferating stromal cells from human carcinomas.

BACKGROUND: Stromal cells are a functionally important component of human carcinomas. The aim of this study was to obtain and characterise primary cultures of stromal cells from human carcinomas and the corresponding surrounding normal tissue. METHODS: Primary stromal cell cultures from tumours of lung, oesophagus and pancreas were obtained using a mild tissue dissociation method and a medium for culturing mesenchymal cells. Immunofluorescence staining and western blotting were used to analyse the expression of differentiation markers and selected known oncoproteins in the cell cultures obtai…

Clinical Protocols for the Isolation and Expansion of Mesenchymal Stromal Cells.

SUMMARY: Multipotent mesenchymal stromal cells (MSCs) are currently exploited in numerous clinical trials to investigate their potential in immune regulation, hematopoiesis, and tissue regeneration. The low frequency of MSCs necessitates cell expansion to achieve transplantable numbers. The challenge is to assure safe and high-quality cell production. GMP(Good Manufacturing Practice)-graded cell processing such as cell preparation, culture, and manipulation is mandatory for the progress of such advanced cell therapy. This review summarizes protocols to isolate MSCs from bone marrow and adipose…

Osteogenic gene expression decreases in stromal cells of patients with osteonecrosis.

Nontraumatic osteonecrosis is related to alcohol and glucocorticoid with unknown pathogenesis. Increased adipogenesis decreases bone morphogenetic protein 2 (BMP2) gene expression after glucocorticoid treatment. Lovastatin enhances BMP2 gene expression in rodents, reverses the effects of glucocorticoids on bone, and prevents glucocorticoid-induced osteonecrosis in chickens and humans. We hypothesized patients with osteonecrosis are more susceptible to glucocorticoid treatment than patients without osteonecrosis. Marrow stromal cell cultures from 14 patients with osteonecrosis, and 10 patients

Oxytocin inhibits T-type calcium current of human decidual stromal cells.

CONTEXT: Little is known about the crosstalk between the decidua and myometrium in relation to human labor. The hormone oxytocin (OT) is considered to be a key mediator of uterine contractility during parturition, exerting some of its effects through calcium channels. OBJECTIVE: The objective was to characterize the effect of OT on the T-type calcium channel in human decidual stromal cells before and after the onset of labor. DESIGN: The nystatin-perforated patch-clamp technique was used to record inward T-type calcium current (I(Ca(T))) from acutely dispersed decidual stromal cells obtained…

Mobilization and homing of bone marrow stromal cells in myocardial infarction.

OBJECTIVE: Marrow stromal cells (MSCs) contain multipotent cells, which may participate in the repair of damaged organs. We tested the hypothesis that MSCs are recruited to the heart upon myocardial infarction (MI), and play pathophysiological roles in the healing and adaptation process. METHODS: Donor MSCs from isogenic Lewis rats were harvested, multiplied and labeled with Lac Z reporter gene. Ten million labeled cells were injected intravenously into the recipient rats (n=30). One week later, 10 rats were killed to examine the distribution of the labeled MSCs. Other rats underwent either c…

Marrow stromal cells for cellular cardiomyoplasty: feasibility and potential clinical advantages.

OBJECTIVES: Marrow stromal cells are mesenchymal stem cells able to differentiate into cardiomyocytes in vitro. We tested the hypothesis that marrow stromal cells, when implanted into myocardium, can undergo milieu-dependent differentiation and express cardiomyogenic phenotypes in vivo. METHODS: Isogenic adult rats were used as donors and recipients to simulate autologous transplantation. Marrow stromal cells isolated from donor leg bones were culture-expanded, labeled with 4;,6-diamidino-2-phenylindole, and then injected into the myocardium of the recipients. The hearts were harvested from 4…

Immunophenotypic features of uterine stromal cells. CD34 expression in endocervical stroma.

CD34 is a myeloid progenitor cell antigen present in endothelial cells and some other mesenchymal cells, including perivascular and periadnexal dermal fibroblasts. It was evaluated immunohistochemically in uterine stromal tissue and in 4 aggressive angiomyxomas and 6 endometrial stromal sarcomas with potentially related and similar stromal tissues. The stromal cells in normal endocervix and endocervical polyps were strongly CD34 positive irrespective of the cycle phase, and negative for muscle actins. Ectocervical stroma was variably but generally less CD34 reactive. In the endometrium, the CD…

Growth and hormonal responsiveness of human endometrial stromal cells in culture.

The present review describes and discusses published results on growth and hormonal responsiveness of human endometrial stromal cells in culture. The proliferative potential of serially subcultured cells, that is, the number of cell doublings before cells enter mitotic senescence and cease to divide, was unusually high in stromal cells from several endometrial specimens, a property that may reflect the unique proliferative capacity of human endometrium when compared to other adult tissues. Fluorescent visualization of microfilaments revealed distinct age-related changes in the distribution of …

[Free stromal cells in dysplasias and cancer of the cervix uteri].

The content and distribution of lymphocytes and plasma cells in stroma was studied in 452 cases of different diseases of the cervix. As dysplastic changes of the epithelium advanced up to the microinvasive form of cancer, the number of lymphocytes was found to increase progressively and blast forms appeared. In intraepithelial cancer, infiltration of the stroma with lymphocytes and plasma cells was poor, whereas in deep invasive cancer no lymphocytic and plasma cell infiltration was observed. The changes in the content and distribution of the immunocompetent cells of the stroma in different st

New therapeutic approaches in pediatric diseases: Mesenchymal stromal cell and mesenchymal stromal cell-derived extracellular vesicles as new drugs.

Mesenchymal Stromal Cell (MSC) clinical applications have been widely reported and their therapeutic potential has been documented in several diseases. MSCs can be isolated from several human tissues and easily expanded in vitro, they are able to differentiate in a variety of cell lineages, and they are known to interact with most immunological cells, showing immunosuppressive and tissue repair properties. Their therapeutic efficacy is closely associated with the release of bioactive molecules, namely Extracellular Vesicles (EVs), effective as their parental cells. EVs isolated from MSCs act b

Mesenchymal Stromal Cells in Pediatric Hematopoietic Cell Transplantation a Review and a Pilot Study in Children Treated With Decidua Stromal Cells for Acute Graft-versus-Host Disease.

Mesenchymal stromal cells (MSCs) are rare precursors in all organs of the body. MSCs have profound anti-inflammatory effects and reduce alloreactivity in vitro and in vivo. In pediatric allogeneic hematopoietic cell transplantation (HCT), MSCs have mainly been used to treat acute graft-versus-host disease (GVHD). MSCs are commercially available for this indication in Canada, Japan, and New Zeeland. More rare indications for MSCs in pediatric patients include graft failure and chronic GVHD. MSCs from bone marrow, adipose tissue, umbilical cord, Wharton's jelly, placenta tissue, and decidua have…

Stromal cells cultivated from the choroid of human eyes display a mesenchymal stromal cell (MSC) phenotype and inhibit the proliferation of choroidal vascular endothelial cells in vitro.

Mesenchymal stromal cells (MSC), with progenitor cell and immunological properties, have been cultivated from numerous vascularized tissues including bone marrow, adipose tissue and the corneal-limbus of the eye. After observing mesenchymal cells as contaminants in primary cultures of vascular endothelial cells derived from the choroidal tunic of the human eye, we investigated whether the choroid might also provide a source of cultured MSC. Moreover, we examined the effect of the choroidal stromal cells (Ch-SC) on the proliferation of freshly isolated choroidal vascular endothelial cells (ChVE…