Autologous Bone Marrow Mononuclear Cell Transplantation Therapy Improved Symptoms in Patients with Refractory Diabetic Sensorimotor Polyneuropathy via the Mechanisms of Paracrine and Immunomodulation: A Controlled Study

We recently reported that transplantation of autologous bone marrow mononuclear cells (BM-MNCs) may be an effective and promising therapy to treat refractory diabetic sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes mellitus (T2DM). This study was designed to investigate the potential mechanisms of BM-MNCs therapy, which recruited 60 patients with DSPN, 30 T2DM patients without complications, and 30 healthy control participants. All clinical parameters, the levels of inflammatory markers, and growth factors in the three groups were compared. Patients in DSPN group had higher level of tumor necrosis factor-α (TNF-α) (DSPN vs control, 412.90 ± 64.58 vs 374.81 ± 63.18 pg/mL, P < 0.01) and lower level of vascular endothelial growth factor (VEGF) (DSPN vs control, 140.93 ± 24.78 vs 157.39 ± 25.11 pg/mL, P < 0.01) than those in control group. DSPN group had the highest level of soluble intercellular adhesion molecule-1 (sICAM-1) among three groups (DSPN and DM vs control, 1477.56 ± 228.00 and 1342.17 ± 237.54 vs 1308.00 ± 200.94 ng/mL, P < 0.05). The level of nerve growth factor in the DSPN group was slightly lower than that in the DM group (DSPN vs DM, 3509.11 ± 438.39 vs 3734.87 ± 647.50 pg/mL, P < 0.05). All patients with DSPN received one intramuscular injection of BM-MNCs and clinical follow-ups after the therapy for 2 days, 1, 4, 12, 24, and 48 weeks. Neuropathic symptoms of foot pain, numbness, and weakness were significantly improved within 4 weeks after BM-MNCs injection. Patients with DSPN were divided into the responder ( n = 35) and nonresponder groups ( n = 19) based on the improvement of nerve conduction velocity at 12 weeks post-transplantation. Compared with nonresponders, responders were younger (57.3 ± 5.2 vs 62.0 ± 4.8, P < 0.01), had a shorter history of diabetes (7.1 ± 2.7 vs 11.2 ± 5.4 years, P < 0.01), and had higher numbers of mobilized CD34+ cells (17.61 ± 2.64 vs 14.79 ± 1.62 ×105/L, P < 0.01) and BM-MNCs (12.05 ± 2.16 vs 9.84 ± 1.53 ×108/L, P < 0.01). The levels of TNF-α and sICAM-1 decreased just after BM-MNCs injection in both groups and slowly reverted to baseline levels. The duration of the downtrend of TNF-α and sICAM-1 in the responder group lasted longer than that in the nonresponder group. Serum level of VEGF in the responder group increased immediately after BM-MNC therapy and reached the highest point after the injection for 12 weeks. On the other hand, VEGF levels in the nonresponder group only increased slightly. Binary logistic regression was performed to evaluate the corresponding prognostic factors for BM-MNCs treatment. The number of applied CD34+ cells and the duration of diabetes were the independent predictors of responding to BM-MNCs therapy. No adverse event associated with the treatment was observed during follow-up observations. These results indicated that BM-MNCs transplantation is an effective and promising therapeutic strategy to treat refractory DSPN. The immune regulation and paracrine function of BM-MNCs may contribute to the improvement of DSPN. Trial registration: Chinese Clinical Trial Registry, ChiCTR-TRC-12002570. URL: http://www.chictr.org.cn/showproj.aspx?proj=6981

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Autologous bone marrow mononuclear cell transplantation therapy improved symptoms in patients with refractory diabetic peripheral neuropathy via the mechanisms of paracrine and immunomodulation

10.21203/rs.3.rs-22717/v1 ◽

2020 ◽

Author(s):

Wei Wei ◽

Li Li ◽

Lin Deng ◽

Zhong-jing Wang ◽

Jing-jian Dong ◽

...

Keyword(s):

Bone Marrow ◽

Peripheral Neuropathy ◽

Growth Factor ◽

Diabetic Peripheral Neuropathy ◽

Autologous Bone Marrow ◽

Control Group ◽

Bone Marrow Mononuclear Cell ◽

Cd34 Cells ◽

Tnf Α ◽

Autologous Bone

Abstract Background: We recently reported that transplantation of autologous bone marrow mononuclear cells (BM-MNCs) may be an effective and promising therapy to treat refractory diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). This study was designed to investigate the potential mechanisms of BM-MNCs therapy.Methods: This clinical study recruited 60 patients with DPN, 30 T2DM patients without complications, 30 healthy control participants. All clinical parameters, the levels of inflammatory markers and growth factors in three groups were compared. All patients with DPN received one intramuscular injection of BM-MNCs and clinical follow-ups after the therapy for 2 days, 1, 4, 12, 24, and 48 weeks. Then they were divided into the responder and non-responder groups based on the improvement of nerve conduction velocity. Binary logistic regression was performed to evaluate the corresponding prognostic factors for BM-MNCs treatment.Results: Patients in DPN group had higher level of tumor necrosis factor-α (TNF-α) and lower level of vascular endothelial growth factor (VEGF) than those in control group. DPN group had the highest level of soluble intercellular adhesion molecule-1 (sICAM-1) among three groups. The level of nerve growth factor (NGF) in DPN group was slightly lower than that in DM group. Neuropathic symptoms were significantly improved after BM-MNCs injection. Thirty five of 54 patients with DPN (64.8%) reached the primary endpoint, and were regarded as the responders. Compared to non-responders, responders were younger, had a longer history of diabetes, and had higher numbers of mobilized CD34+ cells and BM-MNCs. The levels of TNF-α and sICAM-1 decreased just after BM-MNCs injection in both groups and slowly reverted to baseline levels. The durations of downtrend of TNF-α and sICAM-1 in responder group lasted longer than that in non-responder group. Serum level of VEGF in responder group increased immediately after BM-MNC therapy, and reached the highest point after the injection for 12 weeks. On the other hand, VEGF levels in the non-responder group only increased slightly. The number of applied CD34+ cells (OR=1.567, 95% CI 1.106-2.222, p=0.012) and duration of diabetes (OR=0.760, 95% CI 0.597-0.967, p=0.025) were the independent predictors of responding to BM-MNCs therapy. No adverse event associated with the treatment was observed during follow-up observations.Conclusions: BM-MNCs transplantation is an effective and promising therapeutic strategy to treat refractory DPN. The immune regulation and paracrine function of BM-MNCs may contribute to the improvement of DPN.

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Clinical observations of bone marrow transfusion for promoting bone marrow reconstruction after chemotherapy for AIDS-related lymphoma

BMC Immunology ◽

10.1186/s12865-021-00399-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yixuan Liu ◽

Suhong Xie ◽

Lei Li ◽

Yanhui Si ◽

Weiwei Zhang ◽

...

Keyword(s):

Bone Marrow ◽

Immune System ◽

T Lymphocytes ◽

Peripheral Blood ◽

Autologous Bone Marrow ◽

Control Group ◽

Peripheral Vein ◽

Significant Difference ◽

Autologous Bone ◽

Aids Related Lymphoma

Abstract Background This study investigates the effect of autologous bone marrow transfusion (BMT) on the reconstruction of both bone marrow and the immune system in patients with AIDS-related lymphoma (ARL). Methods A total of 32 patients with ARL participated in this study. Among them, 16 participants were treated with conventional surgery and chemotherapy (control group) and the remaining 16 patients were treated with chemotherapy followed by autologous bone marrow transfusion via a mesenteric vein (8 patients, ABM-MVI group) or a peripheral vein (8 patients, ABM-PI group). Subsequently, peripheral blood and lymphocyte data subsets were detected and documented in all patients. Results Before chemotherapy, no significant difference in indicators was observed between three groups of ARL patients. Unexpectedly, 2 weeks after the end of 6 courses of chemotherapy, the ABM-MVI group, and the ABM-PI group yielded an increased level of CD8+T lymphocytes, white blood cells (WBC), and platelet (PLT) in peripheral blood in comparison to the control group. Notably, the number of CD4+T lymphocytes in the ABM-PI group was significantly higher than that in the other two groups. Additionally, no significant difference in haemoglobin levels was observed before and after chemotherapy in both the ABM-MVI and ABM-PI groups, while haemoglobin levels in the control group decreased significantly following chemotherapy. Conclusions Autologous bone marrow transfusion after chemotherapy can promote the reconstruction of both bone marrow and the immune system. There was no significant difference in bone marrow recovery and reconstruction between the mesenteric vein transfusion group and the peripheral vein transfusion group.

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Autologous bone marrow mononuclear cell implantation therapy is an effective limb salvage strategy for patients with severe peripheral arterial disease

Journal of Vascular Surgery ◽

10.1016/j.jvs.2015.02.059 ◽

2015 ◽

Vol 62 (3) ◽

pp. 673-680 ◽

Cited By ~ 16

Author(s):

Randall W. Franz ◽

Kaushal J. Shah ◽

Richard H. Pin ◽

Thomas Hankins ◽

Jodi F. Hartman ◽

...

Keyword(s):

Bone Marrow ◽

Peripheral Arterial Disease ◽

Limb Salvage ◽

Mononuclear Cell ◽

Autologous Bone Marrow ◽

Arterial Disease ◽

Bone Marrow Mononuclear Cell ◽

Autologous Bone ◽

Peripheral Arterial ◽

Cell Implantation

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Efficacy of Autologous Bone Marrow Mononuclear Cell Therapy in Patients with Peripheral Arterial Disease

Journal of Atherosclerosis and Thrombosis ◽

10.5551/jat.23374 ◽

2014 ◽

Vol 21 (11) ◽

pp. 1183-1196 ◽

Cited By ~ 23

Author(s):

Zheng-Xu Wang ◽

Duo Li ◽

Jun-Xia Cao ◽

Yi-Shan Liu ◽

Min Wang ◽

...

Keyword(s):

Bone Marrow ◽

Peripheral Arterial Disease ◽

Cell Therapy ◽

Mononuclear Cell ◽

Autologous Bone Marrow ◽

Arterial Disease ◽

Bone Marrow Mononuclear Cell ◽

Autologous Bone ◽

Peripheral Arterial

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Efficacy of autologous bone marrow mononuclear cells plus mesenchymal stem cell versus autologous bone marrow mononuclear cell alone in ischemic foot ulcer

Cytotherapy ◽

10.1016/j.jcyt.2014.01.285 ◽

2014 ◽

Vol 16 (4) ◽

pp. S77-S78

Author(s):

H. Harunarashid ◽

M. Mohd Idris ◽

F. Mohamad Yusoff ◽

S. Chin ◽

S. Shahari ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Mononuclear Cells ◽

Foot Ulcer ◽

Autologous Bone Marrow ◽

Bone Marrow Mononuclear Cell ◽

Bone Marrow Mononuclear Cells ◽

Autologous Bone ◽

Cell Versus

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Tendon-to-Bone Healing in a Rat Extra-articular Bone Tunnel Model: A Comparison of Fresh Autologous Bone Marrow and Bone Marrow–Derived Mesenchymal Stem Cells

The American Journal of Sports Medicine ◽

10.1177/0363546519862284 ◽

2019 ◽

Vol 47 (11) ◽

pp. 2729-2736

Author(s):

Jun Lu ◽

Connie S. Chamberlain ◽

Ming-liang Ji ◽

Erin E. Saether ◽

Ellen M. Leiferman ◽

...

Keyword(s):

Bone Marrow ◽

Bone Healing ◽

Macrophage Polarization ◽

Group Versus ◽

Autologous Bone Marrow ◽

Bone Tunnel ◽

Control Group ◽

M2 Macrophage ◽

Bone Interface ◽

Autologous Bone

Background: Despite widespread acceptance of fresh autologous bone marrow (BM) for use in clinical practice, limited information exists to analyze if tendon-to-bone healing could be accelerated with local use of fresh autologous BM. Purpose: To investigate the effect of fresh autologous BM on tendon-to-bone healing with a novel rat model. Study Design: Controlled laboratory study. Methods: An extra-articular bone tunnel was created and filled with an autologous tendon graft in skeletally mature Sprague-Dawley rats (N = 60). They were then randomly divided into 3 groups: BM group (injection of fresh autologous BM into the tendon-bone interface, n = 20), BM-derived mesenchymal stem cell (BMSC) group (injection of allogenic cultured BMSCs, n = 20), and the control group (tendon-bone interface without injection of BM or BMSCs, n = 20). Biomechanical, histological, and immunohistochemical analyses were performed at 2 and 6 weeks after surgery. Results: The BM group showed a relatively well-organized and dense connective tissue interface with better orientation of collagen fibers as compared with the BMSC group. At 2 weeks, the tendon-bone interface tissue thickness of the BMSC group was 140 ± 25 μm (mean ± SEM), which was significantly greater than the BM group (58 ± 15 μm). The BM group showed fewer M1 macrophages at the tendon-bone interface at 2 and 6 weeks ( P < .001). In contrast, there were more M2 macrophages at the interface in the BM group 2 and 6 weeks postoperatively when compared with controls and the BMSC group ( P < .001). Biomechanical tests revealed significantly higher stiffness in the BM group versus the control and BMSC groups at 2 and 6 weeks after surgery ( P < .05). Load to failure showed similar trends to stiffness. Conclusion: These findings indicate that local delivery of fresh autologous BM enhances tendon-to-bone healing better than the alternative treatments in this study. This effect may be partially due to the observed modulation of inflammatory processes, especially in M2 macrophage polarization. Clinical Relevance: Fresh autologous BM could be a treatment option for this disorder.

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Repeated Autologous Bone Marrow Transfusion through Portal Vein for Treating Decompensated Liver Cirrhosis after Splenectomy

Gastroenterology Research and Practice ◽

10.1155/2018/4136082 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8

Author(s):

Weiwei Zhang ◽

Mujian Teng ◽

Baochi Liu ◽

Qiling Liu ◽

Xin Liu ◽

...

Keyword(s):

Bone Marrow ◽

Liver Cirrhosis ◽

Liver Function ◽

Portal Vein ◽

Liver Stiffness ◽

Autologous Bone Marrow ◽

Control Group ◽

Decompensated Liver Cirrhosis ◽

Autologous Bone ◽

The Impact

Objective. This study is aimed at examining the impact of repeated intraportal autologous bone marrow transfusion (ABMT) in patients with decompensated liver cirrhosis after splenectomy. Methods. A total of 25 patients with decompensated liver cirrhosis undergoing splenectomy were divided into ABMT and control groups. The portal vein was cannulated intraoperatively using Celsite Implantofix through the right gastroomental vein. Both groups were given a routine medical treatment. Then, 18 mL of autologous bone marrow was transfused through the port in the patients of the ABMT group 1 week, 1 month, and 3 months after laminectomy, while nothing was given to the control group. All patients were monitored for adverse events. Liver function tests, including serum albumin (ALB), alanine aminotransferase (ALT), total bilirubin (TB), prothrombin activity (PTA), cholinesterase (CHE), α-fetoprotein (AFP), and liver stiffness measurement (LSM), were conducted before surgery and 1, 3, and 6 months after surgery. Results. Significant improvements in ALB, ALT, and CHE levels and decreased LSM were observed in the ABMT group compared with those in the control group (P<0.05). TB and PTA improved in both groups but with no significant differences between the groups. No significant changes were observed in AFP in the control group, but it decreased in the ABMT group. No major adverse effects were noted during the follow-up period in the patients of either group. Conclusions. Repeated intraportal ABMT was clinically safe, and liver function of patients significantly improved. Therefore, this therapy has the potential to treat patients with decompensated liver cirrhosis after splenectomy. This trial was registered with the identification number of ChiCTR-ONC-17012592.

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