Umbilical cord mesenchymal stem cell transplantation significantly improves neurological function in patients with sequelae of traumatic brain injury

Wang, Sen; Cheng, Hao‐Tsai; Dai, Guohao; Wang, Xiaodong; Hua, Rongrong; Liu, Xuebin; Wang, Peishen; Chen, Guangming; Yue, Wu; An, Yu

doi:10.1016/j.brainres.2013.08.001

Cited by 138 publications

(125 citation statements)

References 41 publications

Supporting

Mentioning

119

Contrasting

Unclassified

Order By: Relevance

“…HUCB-derived MSCs also were found to stimulate the injured brain of TBI mice, evoking trophic events and the phenotypic switch of microglia/ macrophages, inhibiting glial scarring and leading to significant improvement of neurological outcomes. 25 Currently, a variety of MSCs, 8 including HUCB-derived MSCs, 24,25 represent the most active stem cell population used for pre-clinical and clinical trials of brain injury. While the majority of these regenerative clinical trials using MSCs have proved safety, phase II clinical trials are still ongoing and are facing issues of efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…The therapeutic potential of whole HUCB and derived mononuclear cells (MNCs) in neurological disorders was investigated in animal models of central nervous system damage induced by hemorrhagic brain injury, 19 heatstroke, 20 middle cerebral artery occlusion stroke model, 21 spinal cord injury, 22 as well as TBI. 23 Given the fact that mesenchymal stem cells (MSCs) are frequently used for cell therapy of neurodegenerative disorders in clinical trials, 8,24 a recent study demonstrated the efficacy of HUCBderived MSCs in protecting mice brains after trauma. 25 However, the percentage of MSCs in HUCB is very low and their purification requires multiple cell-sorting steps, presenting a serious disadvantage for translation of this concept into a clinical relevance.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Arien‐Zakay

Gincberg

Nagler³

et al. 2014

Journal of Neurotrauma

View full text Add to dashboard Cite

Treatment of traumatic brain injury (TBI) is still an unmet need. Cell therapy by human umbilical cord blood (HUCB) has shown promising results in animal models of TBI and is under evaluation in clinical trials. HUCB contains different cell populations but to date, only mesenchymal stem cells have been evaluated for therapy of TBI. Here we present the neurotherapeutic effect, as evaluated by neurological score, using a single dose of HUCB-derived mononuclear cells (MNCs) upon intravenous (IV) administration one day post-trauma in a mouse model of closed head injury (CHI). Delayed (eight days post-trauma) intracerebroventricular administration of MNCs showed improved neurobehavioral deficits thereby extending the therapeutic window for treating TBI. Further, we demonstrated for the first time that HUCBderived pan-hematopoietic CD45 positive (CD45 + ) cells, isolated by magnetic sorting and characterized by expression of CD45 and CD11b markers (96-99%), improved the neurobehavioral deficits upon IV administration, which persisted for 35 days. The therapeutic effect was in a direct correlation to a reduction in the lesion volume and decreased by pre-treatment of the cells with anti-human-CD45 antibody. At the site of brain injury, 1.5-2 h after transplantation, HUCBderived cells were identified by near infrared scanning and immunohistochemistry using anti-human-CD45 and antihuman-nuclei antibodies. Nerve growth factor and vascular endothelial growth factor levels were differentially expressed in both ipsilateral and contralateral brain hemispheres, thirty-five days after CHI, measured by enzyme-linked immunosorbent assay. These findings indicate the neurotherapeutic potential of HUCB-derived CD45+ cell population in a mouse model of TBI and propose their use in the clinical setting of human TBI.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Arien‐Zakay

Gincberg

Nagler³

et al. 2014

Journal of Neurotrauma

View full text Add to dashboard Cite

show abstract

“…UC-MSCs also provide a pool of varying kinds of growth factors, including matrix metalloproteinase-2, matrix metalloproteinase-9, hepatocyte growth factor, transforming growth factor β1, granulocyte-colony stimulating factor, fibroblast growth factor 2 and interleukin-6 (Santos et al, 2015). Based on these mechanisms, Zanier et al have suggested that UC-MSCs can protect the murine brain after trauma (Zanier et al, 2011) and impact traumatic brain injury in humans (Wang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Xenotransplantation of human umbilical cord derived stem cells for treatment of type 1 diabetes mellitus in mice

et al. 2016

View full text Add to dashboard Cite

Introduction: Type 1 diabetes mellitus disease (T1D) is an autoimmune disease in which pancreatic islets are attacked by the host's immune system. Although this disease can be treated using some of the current methods, resistance to therapy can develop over time after a long usage of the treatments. Therefore, new strategies to treat T1D have been suggested. This study aims to treat T1D using a new approach to target this autoimmune disease; the approach involves the use of mesenchymal stem cells (MSCs) to induce immune modulation. Methods: Umbilical cord derived MSCs (UC-MSCs) were evaluated in this study. The cells were confirmed to be MSCs by surface profile markers and by in vitro differentiation potential into osteoblasts, adipocytes and chondroblasts. The MSCs were evaluated in a Type 1 diabetic mouse model (induced by streptozotocin (STZ)); MSCs were xenografted at a dose of 2.10 6 cells per mouse in 100 uL of saline. T1D mice injected with saline were used as placebo. Mice were monitored for body weight, blood glucose, blood insulin, glucose tolerance test and pancreas histological analysis. Results: Results showed that UC-MSC xenotransplantation could improve diabetes in mice. Mouse body weight significantly increased after 6 weeks of treatment. Blood glucose levels markedly decreased while blood insulin levels strongly increased towards normal range. Recovery of the insulin positive Langerhans cells was confirmed by histological analysis. Conclusion: Overall, our findings suggest that UC-MSC transplantation is a promising therapy for T1D treatment.

show abstract

“…However, the capability of self-recovery is weak due to the limited quantity of a patient's own stem cells. Therefore, exogenous stem cell transplantation provides a novel method of promoting the recovery of neurological function in patients with TBI (10).…”

Section: Discussionmentioning

confidence: 99%

Acute promyelocytic leukemia following autologous bone marrow-derived mesenchymal stem cell transplantation for traumatic brain injury: A case report

Song

2015

Oncology Letters

View full text Add to dashboard Cite

Abstract. Acute myeloid leukemia (AML) is an extremely rare complication that can be observed following mesenchymal stem cells (MSC) transplantation for traumatic brain injury (TBI). Few cases have been reported thus far. The present study reports a case of acute promyelocytic leukemia (APL) following MSC transplantation in a 36-year-old female. The patient presented with a fever and dermatorrhagia with an associative abnormal coagulation test almost 2 months after the MSC transplantation for TBI. The routine blood test, bone marrow (BM) test, and examination of the promyelocytic leukemia/retinoic acid receptor-α and mixed lineage leukemia chimeric genes confirmed the diagnosis of APL and disseminated intravascular coagulation (DIC). The patient was treated with all-trans retinoic acid to induce remission and cryoprecipitate transfusion for the coagulation abnormality. However, the patient succumbed to the DIC shortly after treatment. To the best of our knowledge, this is the first report of the early occurrence of APL in a patient who received autologous BM-derived MSC therapy for TBI.

show abstract

Umbilical cord mesenchymal stem cell transplantation significantly improves neurological function in patients with sequelae of traumatic brain injury

Cited by 138 publications

References 41 publications

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Xenotransplantation of human umbilical cord derived stem cells for treatment of type 1 diabetes mellitus in mice

Acute promyelocytic leukemia following autologous bone marrow-derived mesenchymal stem cell transplantation for traumatic brain injury: A case report

Contact Info

Product

Resources

About

Umbilical cord mesenchymal stem cell transplantation significantly improves neurological function in patients with sequelae of traumatic brain injury

Cited by 138 publications

References 41 publications

Neurotherapeutic Effect of Cord Blood Derived CD45+Hematopoietic Cells in Mice after Traumatic Brain Injury

Neurotherapeutic Effect of Cord Blood Derived CD45+Hematopoietic Cells in Mice after Traumatic Brain Injury

Xenotransplantation of human umbilical cord derived stem cells for treatment of type 1 diabetes mellitus in mice

Acute promyelocytic leukemia following autologous bone marrow-derived mesenchymal stem cell transplantation for traumatic brain injury: A case report

Contact Info

Product

Resources

About

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury

Neurotherapeutic Effect of Cord Blood Derived CD45⁺Hematopoietic Cells in Mice after Traumatic Brain Injury