BACKGROUND: Owing to the multifactorial nature of the pathogenesis of diabetic peripheral neuropathy (DPN), conventional drug therapies have not been effective. The application of stem cells transplantation may be useful for the treatment of DPN. This study was designed to assess the safety and therapeutic effects of autologous bone marrow mononuclear cells (BMMNCs) transplantation on the treatment of refractory DPN. METHODS: One hundred and sixty-eight patients with refractory DPN were recruited and enrolled in the study. They received intramuscular injection of BMMNCs and followed at 1, 3, 6, 12, 18, 24, and 36 months after the transplantation. Clinical data, Toronto Clinical Scoring System (TCSS), and nerve conduction studies (NCSs) were compared before and after the transplantation. RESULTS: The signs and symptoms of neuropathy were significantly improved after BMMNCs transplantation. The values of the TCSS scores at 1 month (9.68 ± 2.49 vs. 12.55 ± 2.19, P < 0.001) and 3 months (8.47 ± 2.39 vs. 12.55 ± 2.19, P < 0.001) after the treatment reduced significantly compared with the baseline value. This decrement remained persistent until the end of the study. The conduction velocity and action potential and sensory nerves were significantly improved after transplantation (3 and 12 months after the treatment vs. the baseline: motor nerve conduction velocity, 40.24 ± 2.80 and 41.00 ± 2.22 m/s vs. 38.21 ± 2.28 m/s, P < 0.001; sensory nerve conduction velocity, 36.96 ± 2.26 and 39.15 ± 2.61 m/s vs. 40.41 ± 2.22 m/s, P < 0.001; compound muscle action potential, 4.67 ± 1.05 and 5.50 ± 1.20 μV vs. 5.68 ± 1.08 μV, P < 0.001; sensory nerve action potential, 4.29 ± 0.99 and 5.14 ± 1.26 μV vs. 5.41 ± 1.14 μV, P < 0.001). No adverse event associated with the treatment was observed during the follow-up period. CONCLUSIONS Autologous transplantation of BMMNCs may be an effective and promising therapeutic strategy for the treatment of refractory DPN.
Adult ; Aged ; Aged, 80 and over ; Bone Marrow Transplantation ; methods ; Diabetic Neuropathies ; therapy ; Female ; Humans ; Leukocytes, Mononuclear ; cytology ; physiology ; Male ; Middle Aged ; Transplantation, Autologous ; methods

OBJECTIVEWe explored the expressions of the Notch and Wnt signaling pathways and their significance in the repair process of alveolar bone defects by establishing animal models with a composite of autologous bone marrow mesenchymal stem cells (BMSCs) and platelet-rich fibrin (PRF) to repair bone defects in the extraction sockets of rabbits.

METHODSA total of 36 two-month-old male New Zealand white rabbits were randomly divided into four groups, and the left mandibular incisors of all the rabbits were subjected to minimally invasive removalunder general anesthesia. BMSC-PRF compounds, single PRF, and single BMSC were implanted in Groups A, B, and C. No material was implanted in Group D (blank control). The animals were sacrificed at 4, 8 and 12 weeks after surgery, the bone defect was immediately drawn, and the bone specimens underwent surgery after four, eight, and twelve weeks, with three rabbits per time point. The expressions of Notch1 and Wnt3a in the repair process of the bone defect were measured via immunohistochemical and immunofluorescence detection.

RESULTSImmunohistochemistry showed that the expressions of Notch1 and Wnt3a in Groups A, B, and C were higher than that in Group D at the fourth and eighth week after operation (P<0.05). By contrast, the expressions of Notch1 and Wnt3a in Group D were higher than those in Groups A, B, and C at the twelfth week (P<0.05). Immunofluorescence showed that the expressions of both Notch1 and Wnt3a reached their peaks in the new bone cells of the bone defect after four weeks following surgery and gradually disappeared when the bone was repaired completely.

CONCLUSIONNotch1 and Wnt3a signaling molecules are expressed in the process of repairing bone defects using BMSC-PRF composites and can accelerate the healing by regulating the proliferation and differentiation of BMSCs. Moreover, the expressions of Notch and Wnt are similar, and a crosstalk between them may exist it.

Alveolar Bone Grafting ; methods ; Animals ; Blood Platelets ; Bone Marrow Cells ; cytology ; Bone Transplantation ; methods ; Bone and Bones ; abnormalities ; Cell Differentiation ; Fibrin ; administration & dosage ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; Platelet-Rich Plasma ; Rabbits ; Random Allocation ; Receptor, Notch1 ; metabolism ; Tissue Engineering ; Wnt Signaling Pathway ; Wnt3A Protein ; metabolism ; Wound Healing

Bone Marrow Transplantation ; history ; methods ; HLA Antigens ; immunology ; Hematopoietic Stem Cell Transplantation ; history ; methods ; History, 20th Century ; History, 21st Century ; Hospitals, General ; Humans ; Peripheral Blood Stem Cell Transplantation ; history ; methods ; Singapore ; Transplantation Conditioning ; history ; methods

BACKGROUNDSteady-state bone marrow (SS-BM) and granulocyte colony-stimulating growth factor-primed BM/peripheral blood stem-cell (G-BM/G-PBSC) are the main stem-cell sources used in allogeneic hematopoietic stem-cell transplantation. Here, we evaluated the treatment effects of SS-BM and G-BM/G-PBSC in human leucocyte antigen (HLA)-identical sibling transplantation.

METHODSA total of 226 patients (acute myelogenous leukemia-complete remission 1, chronic myelogenous leukemia-chronic phase 1) received SS-BM, G-BM, or G-PBSC from an HLA-identical sibling. Clinical outcomes (graft-versus-host disease [GVHD], overall survival, transplant-related mortality [TRM], and leukemia-free survival [LFS]) were analyzed.

RESULTSWhen compared to SS-BM, G-BM gave faster recovery time to neutrophil or platelet (P < 0.05). Incidence of grade III-IV acute GVHD and extensive chronic GVHD (cGVHD) was lower than seen with SS-BM (P < 0.05) and similar to G-PBSC. Although the incidence of cGVHD in the G-BM group was similar to SS-BM, both were lower than G-PBSC (P < 0.05). G-BM and G-PBSC exhibited similar survival, LFS, and TRM, but were significantly different from SS-BM (P < 0.05). There were no significant differences in leukemia relapse rates among the groups (P > 0.05).

CONCLUSIONSG-CSF-primed bone marrow shared the advantages of G-PBSC and SS-BM. We conclude that G-BM is an excellent stem-cell source that may be preferable to G-PBSC or SS-BM in patients receiving HLA-identical sibling hematopoietic stem-cell transplantation.

Adolescent ; Adult ; Aged ; Bone Marrow ; drug effects ; Bone Marrow Transplantation ; methods ; Child ; Female ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; therapy ; Leukemia, Myeloid, Acute ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Stem Cells ; cytology ; Young Adult

The records of 63 high-risk neuroblastoma patients with bone marrow (BM) tumors at diagnosis were retrospectively reviewed. All patients received nine cycles of induction chemotherapy followed by tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT). Follow-up BM examination was performed every three cycles during induction chemotherapy and every three months for one year after the second HDCT/auto-SCT. BM tumor cells persisted in 48.4%, 37.7%, 23.3%, and 20.4% of patients after three, six, and nine cycles of induction chemotherapy and three months after the second HDCT/auto-SCT, respectively. There was no difference in progression-free survival (PFS) rate between patients with persistent BM tumor and those without during the induction treatment. However, after tandem HDCT/auto-SCT, the PFS rate was worse in patients with persistent BM tumor than in those without (probability of 5-yr PFS 14.7% +/- 13.4% vs. 64.2% +/- 8.3%, P = 0.009). Persistent BM tumor during induction treatment is not associated with a worse prognosis when intensive tandem HDCT/auto-SCT is given as consolidation treatment. However, persistent BM tumor after tandem HDCT/auto-SCT is associated with a worse prognosis. Therefore, further treatment might be needed in patients with persistent BM tumor after tandem HDCT/auto-SCT.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Bone Marrow Neoplasms/pathology/*secondary/*therapy ; Child ; Child, Preschool ; Combined Modality Therapy/methods ; Female ; Humans ; Induction Chemotherapy/methods ; Infant ; Infant, Newborn ; Male ; Neoplasms, Multiple Primary/pathology/*therapy ; Neuroblastoma/*pathology/*therapy ; Prognosis ; Retrospective Studies ; Risk Factors ; Stem Cell Transplantation/*methods ; Treatment Outcome ; Young Adult

PURPOSE: Adipose-derived stem cells (ADSCs) are known to be potentially effective in regeneration of damaged tissue. We aimed to assess the effectiveness of intracoronary administration of ADSCs in reducing the infarction area and improving function after acute transmural myocardial infarction (MI) in a porcine model. MATERIALS AND METHODS: ADSCs were obtained from each pig's abdominal subcutaneous fat tissue by simple liposuction. After 3 passages of 14-days culture, 2 million ADSCs were injected into the coronary artery 30 min after acute transmural MI. At baseline and 4 weeks after the ADSC injection, 99mTc methoxyisobutylisonitrile-single photon emission computed tomography (MIBISPECT) was performed to evaluate the left ventricular volume, left ventricular ejection fraction (LVEF; %), and perfusion defects as well as the myocardial salvage (%) and salvage index. At 4 weeks, each pig was sacrificed, and the heart was extracted and dissected. Gross and microscopic analyses with specific immunohistochemistry staining were then performed. RESULTS: Analysis showed improvement in the perfusion defect, but not in the LVEF in the ADSC group (n=14), compared with the control group (n=14) (perfusion defect, -13.0+/-10.0 vs. -2.6+/-12.0, p=0.019; LVEF, -8.0+/-15.4 vs. -15.9+/-14.8, p=0.181). There was a tendency of reducing left ventricular volume in ADSC group. The ADSCs identified by stromal cell-derived factor-1 (SDF-1) staining were well co-localized by von Willebrand factor and Troponin T staining. CONCLUSION: Intracoronary injection of cultured ADSCs improved myocardial perfusion in this porcine acute transmural MI model.
Adipose Tissue/cytology ; Animals ; Bone Marrow Cells/cytology/*metabolism ; Chemokine CXCL12 ; Coronary Vessels ; Female ; Heart/physiopathology ; Heart Ventricles ; *Mesenchymal Stromal Cells ; Myocardial Infarction/physiopathology/radionuclide imaging/*therapy ; *Stem Cell Transplantation ; Swine ; Technetium Tc 99m Sestamibi/*pharmacology ; Tomography, Emission-Computed, Single-Photon/*methods ; Troponin T ; *Ventricular Function, Left

Bone Marrow Cells ; Hearing Loss, Noise-Induced ; therapy ; Humans ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells

The efficiency of dendritic cell-activated and cytokine-induced killer cell (DC-CIK) therapy on children with acute myeloid leukemia (AML) after chemotherapy was investigated. Mononuclear cells were collected from children achieving complete remission after chemotherapy, cultured in vitro and transfused back into the same patient. Interleukin-2 (IL-2) was injected subcutaneously every other day 10 times at the dose of 1 × 10(6) units. Peripheral blood lymphocyte subsets and minimal residual disease (MRD) were detected by flow cytometry. Function of bone marrow was monitored by methods of morphology, immunology, cytogenetics and molecular biology. The side effects were also observed during the treatment. The average follow-up period for all the 22 patients was 71 months and relapse occurred in two AML patients (9.1%). The percentage of CD3(+)/CD8(+) cells in peripheral blood of 15 patients at the 3rd month after DC-CIK treatment (36.73% ± 12.51%) was dramatically higher than that before treatment (29.20% ± 8.34%, P < 0.05). The MRD rate was >0.1% in 5 patients before the treatment, and became lower than 0.1% 3 months after the treatment. During the transfusion of DC-CIK, side effects including fever, chills and hives appeared in 7 out of 22 (31.82%) cases but disappeared quickly after symptomatic treatments. There were no changes in electrocardiography and liver-renal functions after the treatment. MRD in children with AML can be eliminated by DC-CIK therapy which is safe and has fewer side effects.
Adolescent ; Antineoplastic Agents ; therapeutic use ; Bone Marrow ; drug effects ; immunology ; pathology ; Child ; Child, Preschool ; Cytokine-Induced Killer Cells ; cytology ; immunology ; transplantation ; Dendritic Cells ; cytology ; immunology ; transplantation ; Female ; Humans ; Immunotherapy, Adoptive ; methods ; Injections, Subcutaneous ; Interleukin-2 ; therapeutic use ; Leukemia, Myeloid, Acute ; immunology ; pathology ; therapy ; Male ; Neoplasm, Residual ; Primary Cell Culture ; Recurrence ; Remission Induction ; Treatment Outcome

BACKGROUNDA practical problem impeding clinical translation is the limited bone formation seen in artificial bone grafts. Low-pressure/vacuum seeding and dynamic culturing in bioreactors have led to a greater penetration into the scaffolds, enhanced production of bone marrow cells, and improved tissue-engineered bone formation. The goal of this study was to promote more extensive bone formation in the composites of porous ceramics and bone marrow stromal cells (BMSCs).

METHODSBMSCs/β-tricalcium phosphate (β-TCP) composites were subcultured for 2 weeks and then subcutaneously implanted into syngeneic rats that were split into a low-intensity pulsed ultrasound (LIPUS) treatment group and a control group. These implants were harvested at 5, 10, 25, and 50 days after implantation. The samples were then biomechanically tested and analyzed for alkaline phosphate (ALP) activity and osteocalcin (OCN) content and were also observed by light microscopy.

RESULTSThe levels of ALP activity and OCN content in the composites were significantly higher in the LIPUS group than in the control group. Histomorphometric analysis revealed a greater degree of soft tissue repair, increased blood flow, better angiogenesis, and more extensive bone formation in the LIPUS groups than in the controls. No significant difference in the compressive strength was found between the two groups.

CONCLUSIONLIPUS treatment appears to enhance bone formation and angiogenesis in the BMSCs/β-TCP composites.

Animals ; Bone Marrow Cells ; physiology ; Bone Transplantation ; Calcium Phosphates ; pharmacology ; Male ; Osteogenesis ; physiology ; Rats ; Stromal Cells ; Tissue Engineering ; methods ; Transplantation, Isogeneic ; Ultrasonics ; methods

Bone marrow mesenchymal cells (BMSCs) are regarded as donor cells in cell transplantation therapies for spinal cord injury (SCI) for they have the ability of favourable proliferation and multi-directional differentiation, and are easily isolated and culturd and have less immunological reaction. It has been confirmed that subarachnoid space injection is the most ideal delivery technique of BMSCs. Bone marrow mesenchymal stem cells transplantation is safe and its reconditioning role is certain for SCI in early clinical application. The mechanism of BMSCs promoting functional recovery after SCI is probably concerned with vicarious function, nerve trophism, immunosuppression and promoting axonal regeneration by BMSCs.
Animals ; Bone Marrow Cells ; cytology ; Humans ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology ; Spinal Cord Injuries ; surgery