Bone Marrow Stem Cells Research Articles

ABO incompatibility haploidentical peripheral blood stem cell transplantation combined with a single cord blood unit for severe aplastic anemia patients.

To observe the efficacy of haploidentcial peripheral blood stem cell transplantation combined with a single unrelated cord blood unit for severe aplastic anemia patients with donor-recipient ABO incompatibility. This was a retrospective cohort study and data of 57 severe aplastic anemia patients underwent haploidentical stem cell transplantation from August 1, 2018 to February 28, 2022 in the First Affiliated Hospital of Xi'an Jiaotong University was retrospectively analyzed. All patients were divided into two groups, the donor-recipient ABO matched group (bone marrow+peripheral blood group) using haploidentical bone marrow and peripheral blood stem cells as grafts, and donor-recipient ABO mismatched group (cord blood+peripheral blood group), using unrelated cord blood and haploidentical peripheral blood stem cells as grafts. The differences of hematopoietic reconstitution, acute and chronic graft-versus-host disease, Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection, and overall survival between the two groups were compared. There were 30 cases in cord blood+peripheral blood group and 27 cases in bone marrow+peripheral blood group. One patient in bone marrow+peripheral blood group had primary graft failure, while other patients were successfully implanted. There were no significant differences of neutrophil and platelet recovery rates between two groups. The erythrocyte recovery time of cord blood+peripheral blood group was slower than that of bone marrow+peripheral blood group (p < 0.05). There was no significant difference of the incidence of graft-versus-host disease, CMV, EB virus infection and post-transplant lymphoproliferative disorders between two groups (p > 0.05). The incidence of grade III-IV acute graft-versus-host disease in cord blood+peripheral blood group was higher than that of bone marrow+peripheral blood group (p < 0.05). The incidence of intestinal graft-versus-host disease was higher in minor ABO-mismatched transplantation than that in major ABO-mismatched transplantation (p < 0.05). There was no significant difference of overall survival between two groups (p > 0.05). These findings suggest that haploidentical peripheral blood stem cell transplantation combined with a single cord blood unit may be an alternative option for severe aplastic anemia patients with donor-recipient ABO incompatibility.

Acute myeloid leukemia developed through myeloproliferative features during immunosuppressive therapy for juvenile idiopathic arthritis.

A 17-year-old male with thrombocytosis and exacerbation of arthralgia during intensified immunosuppressive therapy with tocilizumab, prednisolone, and methotrexate for juvenile idiopathic arthritis (JIA) was referred to our department. Bone marrow examination revealed myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U). Peripheral myeloblasts disappeared temporarily after discontinuation of tocilizumab but progressed to acute myeloid leukemia six months after the development of MDS/MPN-U. The patient sustained complete remission after unrelated bone marrow stem cell transplantation, followed by chemotherapy. The arthralgia also improved after chemotherapy. The possibility of developing malignancies during immunosuppressive therapy in patients with JIA should be considered. J. Med. Invest. 71 : 335-339, August, 2024.

Examining the level of inflammatory cytokines TNF-α and IL-8 produced by osteoblasts differentiated from dental pulp stem cells.

The use of dental pulp stem cells (DPSCs) in clinical applications instead of bone marrow stem cells is a very promising method capable of significantly changing the future of medical treatment. If further studies prove that DPSCs and the cells differentiated from them do not stimulate the immune system, these cells can be used more reliably in treatment of autoimmune diseases. In this research, we examined the isolated DPSCs and differentiated osteoblasts from them in medium without inflammatory stimulants in terms of TLR3 and TLR4 gene expression and inflammatory cytokines, including TNF-α and IL-8 using qRT-PCR, and measured the concentration of inflammatory cytokines IL-8 and TNF-α produced by these two types of cells through ELISA. The obtained results showed that the expression level of inflammatory cytokines IL-8 and TNF-α in differentiated osteoblasts is significantly different as compared with DPSCs. However, no significant difference was observed in TLR-4 expression between two groups. An increase in TNF-α expression level was found to directly correlate with an increase in the expression of IL-8. The concentration of cytokine TNF-α in osteoblasts was significantly higher than that of IL-8 in DPSCs. In comparison to DPSCs, osteoblast cells first lead to inflammatory responses. These responses reduce overtime. However, DPSCs retain their immunomodulatory properties and do not show inflammatory responses.

Cartilage regeneration using transforming growth factor-beta 3-loaded injectable crosslinked hyaluronic acid hydrogel.

Cartilage defects can be difficult to heal, potentially leading to complications such as osteoarthritis. Recently, a tissue engineering approach that uses scaffolds and growth factors has been proposed to regenerate new cartilage tissues. Herein, we investigated the application of hyaluronic acid (HA) gel loaded with transforming growth factor-beta 3 (TGF-β3) for enhanced cartilage regeneration. We assessed the clinical conditions required to efficiently enhance the ability of the modified HA gel to repair defective cartilage. Based on our findings, the prepared HA gel exhibited good physicochemical and mechanical properties and was non-toxic and non-inflammatory. Moreover, HA gel-loaded TGF-β3 (HAT) had improved biocompatibility and promoted the synthesis of cartilage-specific matrix and collagen, further improving its ability to repair defects. The application of HAT resulted in an initial burst release of HA, which degraded slowly in vivo. Finally, HAT combined with microfracture-inducing bone marrow stem cells could significantly improve the cartilage microenvironment and regeneration of cartilage defects. Our results indicate that HA is a suitable material for developing growth factor carriers, whereas HAT is a promising candidate for cartilage regeneration. Furthermore, this differentiated strategy provides a rapid and effective clinical approach for next-generation cartilage regeneration.

A surface-independent bioglue using photo-crosslinkable benzophenone moiety.

Surface coating technology is broadly demanded across various fields, including marine and biomedical materials; therefore, a facile and versatile approach is desired. This study proposed an attractive surface coating strategy using photo-crosslinkable benzophenone (BP) moiety for biomaterials application. BP-containing "bioglue" polymer can effectively crosslink with all kinds of surfaces and biomolecules. Upon exposure to ultraviolet (UV) light, free radical reaction from the BP glue facilitates the immobilization of diverse molecules onto different substrates in a straightforward and user-friendly manner. Through either one-step, mixing the bioglue with targeted biomolecules, or two-step methods, pre-coating the bioglue and then adding targeted biomolecules, polyacrylic acid (PAA), cyclic RGD-containing peptides, and proteins (gelatin, collagen, and fibronectin) were successfully immobilized on substrates. After drying the bioglue, targeted biomolecules can still be immobilized on the surfaces preserving their bioactivity. Cell culture on biomolecule-immobilized surfaces using NIH 3T3 fibroblasts and human bone marrow stem cells (hBMSCs) showed significant improvement of cell adhesion and activity compared to the unmodified control in serum-free media after 24 hours. Furthermore, hBMSCs on the fibronectin-immobilized surface showed an increased calcium deposition after 21 days of osteogenic differentiation, suggesting that the immobilized fibronectin is highly bioactive. Given the straightforward protocol and substrate-independent bioglue, the proposed coating strategy is promising in broad-range fields.

Clinical safety and therapeutic efficacy of autologous bone-marrow derived stem cells in restoring glycemic control and treating complications in diabetic patients

Diabetes is one of the most common chronic diseases worldwide, with around 537 million adults aged 20-79 living with the disease. It is a global epidemic and has a rapidly rising incidence. Traditional treatments for diabetes have limited efficacy in achieving long-term disease control. In recent years, the autologous infusion of bone marrow-derived mononuclear cells (BMMNC) has become a novel and effective therapeutic approach in treating autoimmune type 1 diabetes (T1DM). BMMNC contains two important types of stem cells, bone marrow-derived hematopoietic stem cells (BMHSC) and bone marrow-derived mesenchymal stem cells (BMMSC), which are currently used independently or coordinately in the treatment of T1DM. In this review, we summarize the clinical data concerning BMMNC, BMHSC, and BMMSC infusion in patients with diabetes (including type 1, type 2, and secondary diabetes) and diabetes-related complications. Research suggests that the autologous infusion of bone marrow stem cells is safe and effective, offering the potential to be widely used in patients with diabetes.

Combined Light and Thermal Stimulation of Bone Marrow Stem Cells.

Introduction: The purpose of this study is to achieve a significant increase in the proliferative activity of mesenchymal stem cells (MSCs) of the bone marrow (BM) at early passages after laser exposure to a suspension of these cells and to estimate the effect of light and heat components of laser radiation on the proliferation of BM MSCs. Methods: The studies were performed on rats BM MSCs. MSC suspension was placed into the wells and heated by using laser radiation (980 nm wavelength) or a water bath at 70 °C providing similar temperature dynamics. The studies were carried out in 3 comparison groups: (1) control suspension of MSCs, which was not subjected to heating in a water bath or laser exposure; (2) MSC suspension, which was heated for in a water bath; and (3) suspension of MSCs, which was subjected to laser exposure. The exposure times for the 2nd and 3rd experimental groups were 10- 50 seconds. Results: Under optimal parameters of laser action on the suspension of BM MSCs, a six-fold increase in the number of BM MSCs colonies was registered compared to the control. The role of the light and heat components of laser exposure to MSCs was determined by comparable heating of a suspension of BM MSCs in a water bath, at which only a twofold increase in the number of colonies was maximally obtained. Conclusion: The increase in the MSC proliferation activity occurs due to their Thermo-Photobiomodulation. The result obtained is important for practical use in cell transplantation in the treatment of traumatic injuries of bone, cartilage, and tendon tissues when a rapid and multiple increase in the initial number of autologous BM MSCs is required.

Iron chelation improves ineffective erythropoiesis and iron overload in myelodysplastic syndrome mice.

Myelodysplastic syndrome (MDS) is a heterogeneous group of bone marrow stem cell disorders characterized by ineffective hematopoiesis and cytopenias, most commonly anemia. Red cell transfusion therapy for anemia in MDS results in iron overload, correlating with reduced overall survival. Whether the treatment of iron overload benefits MDS patients remains controversial. We evaluate underlying iron-related pathophysiology and the effect of iron chelation using deferiprone on erythropoiesis in NUP98-HOXD13 transgenic mice, a highly penetrant well-established MDS mouse model. Our results characterize an iron overload phenotype with aberrant erythropoiesis in these mice which was reversed by deferiprone-treatment. Serum erythropoietin levels decreased while erythroblast erythropoietin receptor expression increased in deferiprone-treated MDS mice. We demonstrate, for the first time, normalized expression of the iron chaperones Pcbp1 and Ncoa4 and increased ferritin stores in late-stage erythroblasts from deferiprone-treated MDS mice, evidence of aberrant iron trafficking in MDS erythroblasts. Importantly, erythroblast ferritin is increased in response to deferiprone, correlating with decreased erythroblast ROS. Finally, we confirmed increased expression of genes involved in iron uptake, sensing, and trafficking in stem and progenitor cells from MDS patients. Taken together, our findings provide evidence that erythroblast-specific iron metabolism is a novel potential therapeutic target to reverse ineffective erythropoiesis in MDS.

PCAT-1' s role in wound healing impairment: Mitochondrial dysfunction and bone marrow stem cell differentiation inhibition via PKM2/β-catenin pathway and its impact on implant osseo-integration.

This study focused on unravelling the role of PCAT-1 in wound-healing process, particularly its impact on regenerative and osteogenic abilities of mesenchymal stem cells (MSCs). We delved into how PCAT-1 regulates mitochondrial oxidative phosphorylation (OXPHOS) and interacts with pivotal molecular pathways, especially β-catenin and PKM2, using human bone marrow-derived MSCs. MSCs were cultured under specific conditions and PCAT-1 expression was modified through transfection. We thoroughly assessed several critical parameters: MSC proliferation, mitochondrial functionality, ATP production and expression of wound healing and osteogenic differentiation markers. Further, we evaluated alkaline phosphatase (ALP) activity and mineral deposition, essential for bone healing. Our findings revealed that overexpressing PCAT-1 significantly reduced MSC proliferation, hampered mitochondrial performance and lowered ATP levels, suggesting the clear inhibitory effect of PCAT-1 on these vital wound-healing processes. Additionally, PCAT-1 overexpression notably decreased ALP activity and calcium accumulation in MSCs, crucial for effective bone regeneration. This overexpression also led to the reduction in osteogenic marker expression, indicating suppression of osteogenic differentiation, essential in wound-healing scenarios. Moreover, our study uncovered a direct interaction between PCAT-1 and the PKM2/β-catenin pathway, where PCAT-1 overexpression intensified PKM2 activity while inhibiting β-catenin, thereby adversely affecting osteogenesis. This research thus highlights PCAT-1's significant role in impairing wound healing, offering insights into the molecular mechanisms that may guide future therapeutic strategies for enhancing wound repair and bone regeneration.

Study of cell adhesion, osteogenesis, and angiogenesis of a “groove” structure micro-arc oxidation titanium

The use of titanium alloy-based dental implant restorations has gained popularity due to their attractive properties. Current research on the surface modification of titanium materials primarily centers around the surface integration of various metal ions, the incorporation of different drugs, or other materials. By simply adjusting the process parameters of micro-arc oxidation, we were able to form a “groove” structure in titanium chips. Scanning Electron Microscopy (SEM) observations revealed that Bone Marrow Stem Cells (BMSCs) noticeably elongated along the “grooves”. Immunofluorescence results indicated an elevated expression of Osteocalcin (OCN) and CD31 in “groove” structure group. Furthermore, “groove” structure group also amplified the expression of osteogenic genes (Alkaline Phosphatase, ALP; Osteocalcin, OCN) and angiogenic genes (CD31, Vascular Endothelial Growth Factor, VEGF; Angiopoietin-2, ANG2; and Fibroblast Growth Factor, FGF) on the material surface (P < 0.05). This study suggests that the “groove” structure enhances early cell adhesion on the material surface and improves osteogenic and angiogenic differentiation on the titanium surface, thereby providing potential research implications for enhancing the initial stability of implants.

Impact of stem cell selection between bone marrow and peripheral blood stem cells for unrelated hematopoietic stem cell transplantation for hematologic malignancies: on behalf of the Donor/Source Working Group of the Japanese Society for Transplantation and Cellular Therapy

Background aimsThis study aimed to comprehensively assess the impact of stem cell selection between bone marrow (BM) and peripheral blood (PB) in unrelated hematopoietic stem cell transplantation (HSCT) for hematological malignancies. Our objective was to identify specific factors associated with better transplant outcomes. MethodsA retrospective analysis was conducted using data from the Japanese HSCT registry. Inclusion criteria were patients aged 0–70 years who underwent their first unrelated HSCT with BM or PB, with an 8/8 or 7/8 allele HLA match for hematological malignancies between 2010 and 2020. ResultsAmong 10 295 patients, no significant difference was observed in overall survival, relapse, graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) or non-relapse mortality between the groups. Patients who received PB showed no clear difference in acute GVHD but had a greater rate of chronic GVHD, resulting in poor chronic GVHD-free, relapse-free survival (CRFS). Subgroup analyses highlighted the importance of patient-specific factors in source selection. Patients with non-Hodgkin lymphoma and a greater hematopoietic cell transplantation-comorbidity index showed better CRFS and GRFS when BM was the preferred source. Similar trends were observed among patients with standard-risk disease for CRFS. However, no such trends were evident among patients aged 0–24 years, indicating that both sources are viable choices for young patients. ConclusionsThis real-world retrospective analysis showed similar basic outcomes for BM and PB in an unrelated setting. The results support that BM may still be preferred over PB, especially when the long-term quality of life is a major concern. A consideration of individual factors can further optimize transplant success. Further research is warranted to explore the long-term implications of stem cell source selection.

Efficacy of antitumor vaccines based on photoinduced GL261 glioma cells using photosensitizers from the group of tetra(aryl)tetracyanoporphyrases with different aryl substituents

Glioblastomas are solid tumors in the brain that pose a challenge for traditional treatments like surgery, radiation therapy, and chemotherapy. Complete cures are not guaranteed, and these treatments cause numerous side effects. First-line treatment approval has only been granted to Temozolomide (TMZ), the sole chemotherapy drug available. Using TMZ increases the median overall survival from 15 to 17 months. In general clinical practice, innovative interventions have not demonstrated efficacy due to glioma heterogeneity and their immunosuppressive microenvironment. Immunogenic cell death (ICD) activates an immune response against cancer cells by emitting damage-associated molecular patterns (DAMPs) upon cell death/dying. The DAMPs activate an anti-tumor immune response. Photodynamic therapy (PDT) can induce ICD. Integrating the principles of immunogenic cell death into glioma immunotherapy could elicit a targeted immune response against the diverse tumor. Vaccination with dendritic cells represents a promising approach for immunotherapy. The goals of this research are to evaluate the efficacy of a prophylactic vaccine using immunogenically-photoinduced glioma GL261 cells and a dendritic cell vaccine in an orthotopic in vivo model. The glioma cell line (GL261) is cultured in RPMI medium supplemented with 10% serum, L-glutamine, 1% penicillin, and 1% streptomycin in a CO2 incubator. Photodynamic treatment involves using photosensitizers from the tetra(aryl)tetracyanoporphyrazine group with 9-phenanthrenyl (pz I) or 4-(4-fluorobenzyloxy)phenyl (pz III) as side substituents. The GL261 cell line is incubated in a serum-free solution containing a selected porphyrazine for four hours. Subsequently, the solution is exchanged with complete medium and the cells are activated through photodynamic treatment at a dose of 20 J/cm2. The cells are then further incubated for 24 hours in a CO2 incubator. Immunizing mice includes subcutaneously injecting photoinduced GL261 glioma cell lysates twice with a 7-day interval. One week after the final immunization, viable GL261 glioma cells are injected into the brain using a stereotaxis frame. Measuring the neurological status of the animals occurs for 25 days, and tumor localization and volume are detected on day 23 by MRI. The survival rate of the experimental groups was 100% (pz III) or significantly higher (pz I) than that of the control groups. Additionally, neurological symptoms were either not identified (pz III) or were significantly lower (pz I) compared to the control animal groups experienced. The dendritic cell vaccine was based on photoinduced GL261 glioma cells. The femur and tibia bones of C57BL/6J mice were used and differentiated for 9 days in RPMI medium to isolate bone marrow stem cells. The medium was supplemented with 5% fetal bovine serum, 20 ng/ml GM-CSF, 1% L-glutamine, 1mM sodium pyruvate, 50 µM β-mercaptoethanol, 100 units/ml penicillin, and 100 µg/L streptomycin. The culture medium was renewed on days 3 and 6 to maintain stability. Protein levels are quantified in cell lysates collected. 2 mg of protein is added to a dendritic cell suspension, and after 90 minutes, 0.5 µg/ml lipopolysaccharide is added for 24 hours. Intraperitoneal dendritic cell vaccine immunization on animals is conducted, with injections 7 days apart. One week post-last immunization, viable GL261 cells are intracranially injected via a stereotactic frame. The neurological status of the animals was monitored for 25 days, and an MRI was conducted on day 23 to evaluate the brain tumor. The survival rate of animals in the experimental groups did not significantly differ from those in the control groups. However, the experimental groups exhibited significantly lower neurological symptoms, and the tumor was visualized without any areas of necrosis, with a smaller volume.

Comparison of retinal degeneration treatment with four types of different mesenchymal stem cells, human induced pluripotent stem cells and RPE cells in a rat retinal degeneration model

BackgroundRetinal degeneration (RD) is a group of disorders on irreversible vision loss. Multiple types of stem cells were used in clinical trials for RD treatment. However, it remains unknown what kinds of stem cells are most effective for the treatment. Therefore, we investigated the subretinal transplantation of several types of stem cells, human adipose-derived stem cells (hADSCs), amniotic fluid stem cells (hAFSCs), bone marrow stem cells (hBMSCs), dental pulp stem cells (hDPSCs), induced pluripotent stem cell (hiPSC), and hiPSC-derived retinal pigment epithelium (RPE) cells for protection effects, paracrine effects and treatment efficiency in an RD disease model rats.MethodsThe generation and characterization of these stem cells and hiPSC-derived RPE cells were performed before transplantation. The stem cells or hiPSC-derived RPE cell suspension labelled with CellTracker Green to detect transplanted cells were delivered into the subretinal space of 3-week-old RCS rats. The control group received subretinal PBS injection or non-injection. A series of detections including fundus photography, optomotor response (OMR) evaluations, light–dark box testing, electroretinography (ERG), and hematoxylin and eosin (HE) staining of retinal sections were conducted after subretinal injection of the cells.ResultsEach stem cell, hiPSC-derived RPE cell or PBS (blank experiment) was successfully transplanted into at least six RCS rats subretinally. Compared with the control rats, RCS rats subjected to subretinal transplantation of any stem cells except hiPSCs showed higher ERG waves (p < 0.05) and quantitative OMR (qOMR) index values (hADSCs: 1.166, hAFSCs: 1.249, hBMSCs: 1.098, hDPSCs: 1.238, hiPSCs: 1.208, hiPSC-RPE cells: 1.294, non-injection: 1.03, PBS: 1.06), which indicated better visual function, at 4 weeks post-injection. However, only rats that received hiPSC-derived RPE cells maintained their visual function at 8 weeks post-injection (p < 0.05). The outer nuclear layer thickness observed in histological sections after HE staining showed the same pattern as the ERG and qOMR results.ConclusionsCompared to hiPSC-derived RPE cells, adult and fetal stem cells yielded improvements in visual function for up to 4 weeks post-injection; this outcome was mainly based on the paracrine effects of several types of growth factors secreted by the stem cells. Patients with RD will benefit from the stem cell therapy.

Alemtuzumab, Dual Graft-versus-Host Disease Prophylaxis, and Lower CD3+ T Cell Doses Equalize Rates of Acute and Chronic Graft-versus-Host Disease in Pediatric Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation with Matched Unrelated Donor Peripheral Blood Stem Cells or Bone Marrow Grafts

Data comparing hematopoietic stem cell transplantation (HSCT) using bone marrow (BM) or peripheral blood stem cell (PBSC) grafts in children after alemtuzumab-based conditioning are lacking. We investigated whether in vivo T cell depletion using alemtuzumab could reduce the risk of severe acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) after HSCT with matched unrelated donor (MUD) BM or PBSCs. This retrospective multicenter study included 397 children (BM group, n = 202; PBSC group, n = 195) who underwent first MUD HSCT at 9 pediatric centers in the United Kingdom between 2015 and 2019. The median age at transplantation was 7.0 years (range, .1 to 19.3 years), and the median duration of follow-up was 3.1 years (range, .3 to 7.5 years). The 3-year overall survival was 81% for the entire cohort (BM group, 80%; PBSC group, 81%). The incidence of grade II-IV aGVHD was significantly higher in the PBSC group (31%) compared to the BM group (31% versus 19%; P = .003), with no difference in the incidence of grade III-IV aGVHD (BM, 7%; PBSC, 12%; P = .17). CD3+ T cell dose >5 × 108/kg and the use of PBSCs were independent predictors of grade II-IV aGVHD. When considering CD3+ T cell dose and GVHD prophylaxis, PBSC transplantation with a calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) and a CD3+ T cell dose ≤5 × 108/kg had a comparable grade II-IV aGVHD to BM transplantation plus a CNI (20% versus 18%; P = .52). PBSC transplantation was associated with a lower incidence of cGVHD compared to BM transplantation (6% versus 11%; P = .03). Within the limits of this study, we identified a potential strategy to reduce the risk of severe GVHD in pediatric PBSC recipients that includes a combination of in vivo T cell depletion using alemtuzumab and dual GVHD prophylaxis (with a CNI and MMF) and limiting the CD3+ T cell dose to ≤5 × 108/kg.

A sequential physical and chemical dual crosslinked multifunctional hydrogel with enhanced mechanical and osteogenic effects for vascularized bone tissue regeneration

Hydrogels have been recognized for their versatile in regenerative medicine; however, their inadequate mechanical and osteogenic properties have limited their applicability in bone tissue engineering (BTE). Hence, we present a novel approach to address this issue by developing sulfated methacrylate hyaluronic acid hydrogels (SMeHA@CM) doped with alendronate (ALN), calcium ions (Ca2+), and magnesium ions (Mg2+). This hydrogel system incorporates sequential physical and chemical crosslinking to facilitate the treatment of bone defects. Physical crosslinks form between the SO32−, ALN, and Ca2+/Mg2+ ions, resulting in nanocluster crosslinking and complete filling of irregular bone defects. Subsequently, the methacrylate groups within the polymer chain undergo polymerization under ultraviolet light irradiation, forming the second stage of chemical crosslinking in the SMeHA@CM hydrogel. These chemical crosslinks contribute strong chemical bonds, enhancing biomechanical strength, and stable support for bone regeneration. The SMeHA@CM hydrogel exhibits remarkable osteogenic capacity, primarily attributed to the cooperative action of SO32− and Mg2+ ions, which promote the recruitment of bone marrow stem cells and angiogenesis. Furthermore, the sustained release of SO32−-ALN-Ca2+/Mg2+ nanoclusters from the hydrogel system offers additional benefits for bone regeneration. Moreover, both in-vitro and in-vivo assessments confirm the significant potential of the newly developed SMeHA@CM hydrogel for applications in BTE.

Treatment of a non-healing oral wound in diabetic-induced rats

Aim: Non-healing wounds are one of the most substantial and difficult problems to treat. Wound healing involves a sequence of complex biological processes, but often the oral cavity microbiota adversely affects healing and forms a chronic non-healing wound. Methods: In this study, a biologically active membrane (BAM) is present, consisting of decellularized human amniotic membrane and bone marrow stem cells (BMSCs). The efficacy of BAM was evaluated in a model of non-healing oral wounds in rats with streptozotocin (STZ)-induced diabetes mellitus. Results: Studies have shown that BAM enhanced the healing of chronic oral wounds in animals with induced diabetes mellitus, reduced scarring, and reduced risk of infection. Paracrine freeze-dried BMSCs stimulated angiogenesis and improved wound conditions. Conclusions: BMSCs may lower glucose levels in rats with STZ-induced diabetes mellitus and improve the healing process of chronic diseases. However, more studies are needed to study the paracrine factors of BMSCs and their role in the treatment of non-healing wounds.

Using a developed co-culture device to evaluate the proliferation of bone marrow stem cells by stimulation with platelet-rich plasma and electromagnetic field

BackgroundsBone marrow stem cell can differentiate to osteoblast by growth factors, pulsed low-intensity ultrasound and electric magnetic field. In the research, bone marrow stem cells were cultured; bone marrow stem cells in culture can be stimulated by platelet-rich plasma and electric field.MethodsThe culture well of the co-cultivation device has a radius of 7.5 mm and a depth of 7 mm. It is divided into two sub-chambers separated by a 3 mm high and 1 mm wide barrier. The bone marrow stem cells were seeded at a density of 2 × 104 cells and the medium volume was 120μl. Platelet-rich plasma (PRP) or platelet-poor plasma (PPP) was added to the other sub-chamber at a volume of 10μl. The bone marrow stem cells were subjected to different electric fields (0 ~ 1 V/cm) at a frequency of 70 kHz for 60 min.ResultsThe highest osteogenic capacity of bone marrow stem cells was achieved by addition of PRP to electric field stimulation (0.25 V/cm) resulted in a proliferation rate of 599.78%. In electric field stimulation (0.75 V/cm) with PPP, the proliferation rate was only 10.46%.ConclusionsBone marrow stem cell with PRP in the co-culture device combined with electric field at 0.25 V/cm strength significantly promoted the growth of bone marrow stem cells.

Protective Effect of Resveratrol on Cytotoxicity, Genotoxicity, and Oxidative Stress Caused by Cyclophosphamide and Methotrexate in Bone Marrow Stem Cell Line and Blood Lymphocytes of the Rat

Protective Effect of Resveratrol on Cytotoxicity, Genotoxicity, and Oxidative Stress Caused by Cyclophosphamide and Methotrexate in Bone Marrow Stem Cell Line and Blood Lymphocytes of the Rat

BushenHuoxue formula promotes osteogenic differentiation via affecting Hedgehog signaling pathway in bone marrow stem cells to improve osteoporosis symptoms.

The BushenHuoxue formula (BSHX) has been previously demonstrated to ameliorate osteoporosis, but the mechanisms underlying this phenomenon are currently unclear. The present study aims at investigating the mechanisms that BSHX induces osteogenesis. We established an osteoporosis model in rats by bilateral ovariectomy and then treated the rats with an osteogenic inducer (dexamethasone, β-sodium glycerophosphate and Vitamin C) and BSHX. After that, bone marrow density and histopathological bone examination were evaluated by using HE staining and immunohistochemistry, respectively. We also assessed the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts by using immunofluorescence staining. ALP, BMP, and COL1A1 levels were determined by ELISA. We identified genes involved in pathogenesis of osteoporosis through Gene Expression Omnibus (GEO) database and subsequently selected Hedgehog signaling-related genes Shh, Ihh, Gli2, and Runx2 for assessment via qRT-PCR and ELISA, Western blotting. Network pharmacology analysis was performed to identify bioactive metabolites of BSHX. BSHX treatment in osteoporosis model rats promoted tightening of the morphological structure of the trabecular bone and increased the bone mineral density (BMD). BSHX also increased levels of osteoblast makers ALP, BMP, and COL1A1. Additionally, bioinformatics analysis of the GEO dataset showed that Hedgehog signaling pathway was involved in pathogenesis of osteoporosis, especially related genes Shh, Ihh, Gli2, and Runx2. Remarkably, BHSX upregulated these genes indispensably involved in the osteogenesis-related Hedgehog signaling pathway in both bone tissue and BMSCs. Importantly, we identified that quercetin was the active compounds that involved in the mechanism of BSHX-improved OP via affecting Hedgehog-related genes. Our results indicate that BSHX promotes osteogenesis by improving BMSC differentiation into osteoblasts via increased expression of Hedgehog signaling-related genes Shh, Ihh, Gli2, and Runx2, and quercetin was the bioactive compound of BSHX.

ABO Incompatibility Haploidentical Peripheral Blood Stem Cell Transplantation Combined with a Single Cord Blood Unit for Severe Aplastic Anemia Patients

Background: For young severe aplastic anemia (SAA) patients without HLA matched donors, haploidentical hematopoietic stem cell transplantation can be used as an alternative selection. The grafts of classic Beijing protocol in China is a combination of bone marrow and peripheral blood stem cell. For patients with major or minor blood type incompatibility, bone marrow stem cells need to undergo red blood cell or plasma removal treatment. There was rare reports about haploidentical peripheral blood stem cell combined with a single unrelated cord blood unit for ABO incompatibility haploidentical stem cell transplantation in SAA patients. Objective: To observe the efficacy of ABO incompatibility haploidentcial peripheral blood hematopoietic stem cell transplantation combined with a single unrelated cord blood unit for SAA patients. Method s : Fifty-five SAA patients underwent stem cell transplantation from August 2018 to February 2022 in the First Affiliated Hospital of Xi'an Jiaotong Univeristy were divided into two groups based on donor-recipient ABO compatibility, the donor-recipient ABO matched group（BM+PB group）using haploidentical bone marrow and peripheral blood stem cell as grafts, and donor-recipient ABO mismatched group（CB+PB group）, using unrelated cord blood and haploidentical peripheral blood stem cell as grafts. The differences of hematopoietic reconstitution, acute and chronic GVHD, CMV and EB virus infection, PFS, and OS between the two groups were compared. Result s : There were 30 cases in CB+PB group and 27 cases in the BM+PB group. Except for differences in donor-recipient ABO compatibility, the other characteristics of the two groups of patients were comparable((P&amp;gt;0.05). One patient in the BM+PB group had primary graft failure, while the rest of the patients were successfully implanted. There were no significant statistical differences in neutrophil,platelet and red blood cells recovery rates, the incidence of acute and chronic GVHD, CMV, EB virus infection, and PTLD between the two groups of patients(P&amp;gt;0.05). There was no significant statistical difference in OS between the two groups of patients(P&amp;gt;0.05)(Figure 1). Conclusion: For SAA patients with donor-recipient ABO incompatibility could use haploidentical peripheral blood cell combined with unrelated cord blood for transplantation which had compared outcome with haploidentcal bone marrow and peripheral blood cell transplantation.