Bone marrow-derived cells fuse with normal and transformed intestinal stem cells.
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ABSTRACT:
SUBMITTER: Rizvi AZ
PROVIDER: S-EPMC1435365 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNecrotizing enterocolitis (NEC) is a major cause of morbidity in premature infants. However, effective treatment options for NEC are currently lacking.PurposeThis study aimed to determine the optimal dose of intraperitoneally administered bone marrow-derived mesenchymal stem cells (BM-MSCs) and investigate the therapeutic potential of orally administered BM-MSCs in NEC.MethodsNeonatal mice were fed maternal breast milk for the first 2 days of life. On day 3, the neonatal mice were randomly divided into control, negative control, and BM-MSC-treated groups. Lipopolysaccharide (LPS) was administered for 3 days, and cold stress (4°C, 10 minutes) was applied 3 times a day to induce NEC. High-dose (1×106 cells) or low-dose (1×105 cells) BM-MSCs were administered intraperitoneally 1 or 3 times between days 6 and 8 to treat the NEC. The orally administered group received a low dose of BM-MSCs on day 6. Furthermore, except for the control group, intraepithelial cells (IECs) of the small intestine of neonatal mice were treated with LPS and exposed to 5% O2/95% N2 hypoxic stress for 2 hours. Thereafter, each was treated with BM-MSCs.ResultsTissue injury, apoptosis, and inflammatory marker levels were significantly reduced after BM-MSC administration. Oral administration was as effective as intraperitoneal administration, even at a low dose (1×105 cells) of BM-MSCs. The efficacy of high (1×106 cells) or multiple divided doses of BM-MSCs did not differ from that of low-dose treatment. Significantly improved wound healing was observed after BM-MSC administration to injured IECs.ConclusionThe oral administration of BM-MSCs is a promising treatment option for NEC in infants. Further human studies of BM-MSCs are necessary to determine the optimal dose required to achieve safe and effective outcomes.
| S-EPMC10915455 | biostudies-literature
Project description:Hematopoietic stem cells (HSCs) in the endosteum of mesoderm-derived appendicular bones have been extensively studied. Neural crest-derived bones differ from appendicular bones in developmental origin, mode of bone formation and pathological bone resorption. Whether neural crest-derived bones harbor HSCs is elusive. Here, we discovered HSC-like cells in postnatal murine mandible, and benchmarked them with donor-matched, mesoderm-derived femur/tibia HSCs, including clonogenic assay and long-term culture. Mandibular CD34 negative, LSK cells proliferated similarly to appendicular HSCs, and differentiated into all hematopoietic lineages. Mandibular HSCs showed a consistent deficiency in lymphoid differentiation, including significantly fewer CD229?+?fractions, PreProB, ProB, PreB and B220?+?slgM cells. Remarkably, mandibular HSCs reconstituted irradiated hematopoietic bone marrow in vivo, just as appendicular HSCs. Genomic profiling of osteoblasts from mandibular and femur/tibia bone marrow revealed deficiencies in several HSC niche regulators among mandibular osteoblasts including Cxcl12. Neural crest derived bone harbors HSCs that function similarly to appendicular HSCs but are deficient in the lymphoid lineage. Thus, lymphoid deficiency of mandibular HSCs may be accounted by putative niche regulating genes. HSCs in craniofacial bones have functional implications in homeostasis, osteoclastogenesis, immune functions, tumor metastasis and infections such as osteonecrosis of the jaw.
| S-EPMC5175267 | biostudies-literature
Project description:Bone marrow mesenchymal stromal cells (BM-MSCs) have anti-inflammatory and pro-survival properties. Naturally, they do not express human leukocyte antigen class II surface antigens and have immunosuppressive capabilities. Together with their relatively easy accessibility and expansion, they are an attractive tool for organ support in transplantation and regenerative therapy. Autologous BM-MSC transplantation alone or together with transplanted islets improves β-cell function, graft survival, and glycemic control in diabetes. Albeit MSCs' capacity to transdifferentiate into β-cell is limited, their protective effects are mediated mainly by paracrine mechanisms through BM-MSCs circulating through the body. Direct cell-cell contact and spontaneous fusion of BM-MSCs with injured cells, although at a very low rate, are further mechanisms of their supportive effect and for tissue regeneration. Diabetes is a disease of long-term chronic inflammation and cell therapy requires stable, highly functional cells. Several tools and protocols have been developed by mimicking natural fusion events to induce and accelerate fusion in vitro to promote β-cell-specific gene expression in fused cells. BM-MSC-islet fusion before transplantation may be a strategy for long-term islet survival and improved function. This review discusses the cell-protective and anti-inflammatory characteristics of BM-MSCs to boost highly functional insulin-producing cells in vitro and in vivo, and the efficacy of their fusion with β-cells as a path to promote β-cell regeneration.
| S-EPMC9327419 | biostudies-literature
Project description:Mesenchymal stem cells (MSCs) hold great potential in cell therapy and have attracted increasing interests in a wide range of biomedical sciences. However, the scarcity of MSCs and the prolonged isolation procedure limited the clinical application. To address these 2 issues, we developed a method to isolate MSCs from bone biopsy tissues of euthanized canine body donors. Compared to the traditional method to isolate MSCs from aspirated bone marrow (BMSCs), the isolation procedure for MSCs from harvested epiphyseal cancellous bone (EMSCs) was less time-consuming. The isolated EMSCs had similar plastic-adherence, tri-lineage differentiation and consistent surface marker profiles compared to BMSCs. We harvested BMSCs and EMSCs from 24 euthanized cases from clinics and 42 euthanized donors from a local shelter. The successful rate for EMSC isolation is significantly higher compared to BMSC isolation, while the other properties of the isolated MSCs including the clonogenicity, proliferative potentials and molecular phenotypes were not discernibly different between the MSCs established by the two methods. In conclusion, we demonstrated a new procedure to harvest MSCs by bone biopsy at the epiphyseal region. This method is less time consuming and more reliable, and the resulting MSCs are comparable to those harvested by bone marrow aspiration. The combination of the two methods can greatly improve the efficiency to harvest MSCs.
| S-EPMC4383772 | biostudies-literature
Project description:IntroductionBone marrow mesenchymal stem cells (BMMSCs) are a heterogeneous population of postnatal precursor cells with the capacity of adhering to culture dishes generating colony-forming unit-fibroblasts (CFU-F). Here we identify a new subset of BMMSCs that fail to adhere to plastic culture dishes and remain in culture suspension (S-BMMSCs).MethodsTo catch S-BMMSCs, we used BMMSCs-produced extracellular cell matrix (ECM)-coated dishes. Isolated S-BMMSCs were analyzed by in vitro stem cell analysis approaches, including flow cytometry, inductive multiple differentiation, western blot and in vivo implantation to assess the bone regeneration ability of S-BMMSCs. Furthermore, we performed systemic S-BMMSCs transplantation to treat systemic lupus erythematosus (SLE)-like MRL/lpr mice.ResultsS-BMMSCs are capable of adhering to ECM-coated dishes and showing mesenchymal stem cell characteristics with distinction from hematopoietic cells as evidenced by co-expression of CD73 or Oct-4 with CD34, forming a single colony cluster on ECM, and failure to differentiate into hematopoietic cell lineage. Moreover, we found that culture-expanded S-BMMSCs exhibited significantly increased immunomodulatory capacities in vitro and an efficacious treatment for SLE-like MRL/lpr mice by rebalancing regulatory T cells (Tregs) and T helper 17 cells (Th17) through high NO production.ConclusionsThese data suggest that it is feasible to improve immunotherapy by identifying a new subset BMMSCs.
| S-EPMC3580431 | biostudies-literature
Project description:Content and aims: Ginsenoside RG1 (RG1) is thought to enhance proliferation and differentiation of stem cell, however, its role on paracrine efficacy of stem cell remains unclear. Here we examined if and how RG1 enhances the paracrine effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) on radiation induced intestinal injury (RIII).MethodIrradiated rats randomly received intraperitoneal injection of conditioned medium (CM) derived from non-activated BM-MSCs (MSC-CM) or BM-MSCs pre-activated by RG-1 (RG1-MSC-CM). Intestinal samples were collected, followed by the evaluation of histological and functional change, apoptosis, proliferation, inflammation, angiogenesis and stem cell regeneration. The effects of heme oxygenase-1 (HO-1) were investigated using HO-1 inhibitor or siRNA.ResultRG1 enhanced the paracrine efficacy of BM-MSCs partially through upregulation of HO-1. RG1-MSC-CM rather than MSC-CM significantly improved the survival and intestinal damage of irradiated rats via improvement of intestinal proliferation/apoptosis, inflammation, angiogenesis and stem cell regeneration in a HO-1 dependent mechanism. The mechanism for the superior paracrine efficacy of RG1-MSC-CM is related to a higher release of two pivotal cytokines VEGF and IL-6.ConclusionOur study revealed that RG1 enhances paracrine effects of BM-MSCs on RIII, providing a novel method for maximizing the paracrine potential of MSCs.
| S-EPMC7835034 | biostudies-literature
Project description:Pancreatic adenocarcinoma remains one of the most challenging diseases of modern gastroenterology, and, even though considerable effort has been put into understanding its pathogenesis, the exact molecular mechanisms underlying the development and/or systemic progression of this malignancy still remain unclear. Recently, much attention has been paid to the potential role of bone marrow-derived stem cells (BMSCs) in this malignancy. Hence, herein, we comprehensively review the most recent discoveries and current achievements and concepts in this field. Specifically, we discuss the significance of identifying pancreatic cancer stem cells and novel therapeutic approaches involving molecular interference of their metabolism. We also describe advances in the current understanding of the biochemical and molecular mechanisms responsible for BMSC mobilization during pancreatic cancer development and systemic spread. Finally, we summarize experimental, translational, and/or clinical evidence regarding the contribution of bone marrow-derived mesenchymal stem cells, endothelial progenitor cells, hematopoietic stem/progenitor cells, and pancreatic stellate cells in pancreatic cancer development/progression. We also present their potential therapeutic value for the treatment of this deadly malignancy in humans.Different bone marrow-derived stem cell populations contribute to the development and/or progression of pancreatic cancer, and they might also be a promising "weapon" that can be used for anticancer treatments in humans. Even though the exact role of these stem cells in pancreatic cancer development and/or progression in humans still remains unclear, this concept continues to drive a completely novel scientific avenue in pancreatic cancer research and gives rise to innovative ideas regarding novel therapeutic modalities that can be safely offered to patients.
| S-EPMC4922853 | biostudies-other
Project description:Regenerative medicine is a promising field in orthopaedic surgery. Although surgical treatments can produce excellent outcomes and may be the best choice for some patients, regenerative medicine can provide with more minimally-invasive treatment options. Mesenchymal stem cells (MSCs) are multipotent cells and are highly capable to differentiate into osteocytes or chondrocytes, while they can be isolated from different bone sources. The bone marrow aspiration from the posterior iliac crest appears to be preferred, as it provided a modestly higher concentration of nucleated cells [(25.1-54.7)×106 cells/mL]. MSCs are also easily obtained from other bone sources, such as humerus, femur, tibia, vertebral body or calcaneus and have their content ranges between 5.8×106 and 38.7×106 nucleated cells. Although, they present a wide range of documented nucleated cells, they can be cultivated and expanded in vitro in multiple cell types, avoiding a second surgical site while preventing post-operative pain and the possible risk for infection. Thus, they represent a promising and encouraging treatment option in orthopaedic surgery.
| S-EPMC7492710 | biostudies-literature
Project description:Advances in understanding of the maintenance of the cardiac valves during normal cardiac function and response to injury have led to several novel findings, including that there is contribution of extra-cardiac cells to the major cellular population of the valve: the valve interstitial cell (VIC). While suggested to occur in human heart studies, we have been able to experimentally demonstrate, using a mouse model, that cells of bone marrow hematopoietic stem cell origin engraft into the valves and synthesize collagen type I. Based on these initial findings, we sought to further characterize this cell population in terms of its similarity to VICs and begin to elucidate its contribution to valve homeostasis. To accomplish this, chimeric mice whose bone marrow was repopulated with enhanced green fluorescent protein (EGFP) expressing total nucleated bone marrow cells were used to establish a profile of EGFP(+) valve cells in terms of their expression of hematopoietic antigens, progenitor markers, fibroblast- and myofibroblast-related molecules, as well as their distribution within the valves. Using this profile, we show that normal (non-irradiated, non-transplanted) mice have BM-derived cell populations that exhibit identical morphology and phenotype to those observed in transplanted mice. Collectively, our findings establish that the engraftment of bone marrow-derived cells occurs as part of normal valve homeostasis. Further, our efforts demonstrate that the use of myeloablative irradiation, which is commonly employed in studies involving bone marrow transplantation, does not elicit changes in the bone marrow-derived VIC phenotype in recipient mice.
| S-EPMC3208774 | biostudies-literature
Project description:Neoplastic epithelia may remain dormant and clinically unapparent in human patients for decades. Multiple risk factors including mutations in tumor cells or the stromal cells may affect the switch from dormancy to malignancy. Gene mutations, including p53 mutations, within the stroma of tumors are associated with a worse clinical prognosis; however, it is not known if these stromal mutations can promote tumors in genetically at-risk tissue. To address this question, Apc(Min/+) and Apc(Min/+) Rag2(-/-) mice, which have a predilection to mammary carcinoma (as well as wild-type (wt) mice), received mesenchymal stem cells (MSC) with mutant p53 (p53MSC) transferred via tail vein injection. In the wt mouse, p53MSC circulated in the periphery and homed to the marrow cavity where they could be recovered up to a year later without apparent effect on the health of the mouse. No mammary tumors were found. However, in mice carrying the Apc(Min/+) mutation, p53MSC homed to mammary tissue and significantly increased the incidence of mammary carcinoma. Tumor necrosis factor (TNF)-alpha-dependent factors elaborated from mesenchymal cells converted quiescent epithelia into clinically apparent disease. The increased cancer phenotype was completely preventable with neutralization of TNF-alpha or by transfer of CD4(+) regulatory T cells from immune competent donors, demonstrating that immune competency to regulate inflammation was sufficient to maintain neoplastic dormancy even in the presence of oncogenic epithelial and stromal mutations. The significant synergy between host immunity and mesenchymal cells identified here may restructure treatments to restore an anticancer microenvironment.
| S-EPMC3135253 | biostudies-literature