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Intravenous Autologous Bone Marrow Mononuclear Cell Transplantation for Stroke: Phase1/2a Clinical Trial in a Homogeneous Group of Stroke Patients.

Taguchi A, Sakai C, Soma T, Kasahara Y, Stern DM, Kajimoto K, Ihara M, Daimon T, Yamahara K, Doi K, Kohara N, Nishimura H, Matsuyama T, Naritomi H, Sakai N, Nagatsuka K - Stem Cells Dev. (2015)

Bottom Line: Compared with 1 month after treatment, patients receiving cell therapy displayed a trend toward improved cerebral blood flow and metabolic rate of oxygen consumption 6 months after treatment.In comparison with historical controls, patients receiving cell therapy had significantly better neurologic outcomes.Our results indicated that intravenous transplantation of autologous bone marrow mononuclear cells is safe and feasible.

View Article: PubMed Central - PubMed

Affiliation: 1 Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation , Kobe, Japan .

ABSTRACT
The goal of this clinical trial was to assess the feasibility and safety of transplanting autologous bone marrow mononuclear cells into patients suffering severe embolic stroke. Major inclusion criteria included patients with cerebral embolism, age 20-75 years, National Institute of Health Stroke Scale (NIHSS) score displaying improvement of ≤ 5 points during the first 7 days after stroke, and NIHSS score of ≥ 10 on day 7 after stroke. Bone marrow aspiration (25 or 50 mL; N = 6 patients in each case) was performed 7-10 days poststroke, and bone marrow mononuclear cells were administrated intravenously. Mean total transplanted cell numbers were 2.5 × 10(8) and 3.4 × 10(8) cells in the lower and higher dose groups, respectively. No apparent adverse effects of administering bone marrow cells were observed. Compared with the lower dose, patients receiving the higher dose of bone marrow cells displayed a trend toward improved neurologic outcomes. Compared with 1 month after treatment, patients receiving cell therapy displayed a trend toward improved cerebral blood flow and metabolic rate of oxygen consumption 6 months after treatment. In comparison with historical controls, patients receiving cell therapy had significantly better neurologic outcomes. Our results indicated that intravenous transplantation of autologous bone marrow mononuclear cells is safe and feasible. Positive results and trends favoring neurologic recovery and improvement in cerebral blood flow and metabolism by cell therapy underscore the relevance of larger scale randomized controlled trials using this approach.

No MeSH data available.


Related in: MedlinePlus

Comparison between enrolled patients and historical controls at the time of discharge from the hospital. (a) Proportion of the patients with change for the worse in NIHSS score between day 7 after onset of stroke and discharge. (b, c) Significant improvement was observed in patients undergoing cell transplantation in NIHSS score (b, *P < 0.05) and improvement in NIHSS (day 7 after onset of stroke vs discharge) (c, *P < 0.05). (d–f) Although there was no statistical significant difference between groups in the level of mRS (d), ratio of favorable outcome (e), and Barthel Index (d), a trend toward improvement was observed in the cell therapy group in each case, compared with historical controls.
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f6: Comparison between enrolled patients and historical controls at the time of discharge from the hospital. (a) Proportion of the patients with change for the worse in NIHSS score between day 7 after onset of stroke and discharge. (b, c) Significant improvement was observed in patients undergoing cell transplantation in NIHSS score (b, *P < 0.05) and improvement in NIHSS (day 7 after onset of stroke vs discharge) (c, *P < 0.05). (d–f) Although there was no statistical significant difference between groups in the level of mRS (d), ratio of favorable outcome (e), and Barthel Index (d), a trend toward improvement was observed in the cell therapy group in each case, compared with historical controls.

Mentions: Before initiation of this clinical trial, the medical records of 4,953 inpatients were surveyed and 539 cases were identified as acute cerebral embolism. Of the latter, 59 patients matched the entry criteria for our study to receive cell therapy. The mean age and NIHSS scores on days 0 and 7 after stroke were 66.7 ± 9.0, 18.5 ± 5.4, and 20.5 ± 8.3, respectively. The proportion of males was 37% (22/59). There was no significant difference in patient characteristics and outcomes between cell-treated and historical control groups, aside from gender (P < 0.05). Figure 6 shows the comparison of neurologic outcomes at the time of discharge, comparing patients who received cell therapy with historical controls. Although there was no significant difference in the proportion of change for the worse in NIHSS score between groups (Fig. 6a), a trend favoring improvement was observed in the group treated with bone marrow mononuclear cells. Thus, cell therapy did not increase the risk of worsening stroke outcome. Significant differences were observed between the two groups in NIHSS scores at the time discharge (Fig. 6b) (P < 0.05) and change of the NIHSS score between day 7 after onset of stroke and discharge (Fig. 6c) (P < 0.05). No statistical significance was observed in the mRS score (Fig. 6d), proportion of patients with the favorable outcome (Fig. 6e), and the Barthel Index score (Fig. 6f) between the two groups.


Intravenous Autologous Bone Marrow Mononuclear Cell Transplantation for Stroke: Phase1/2a Clinical Trial in a Homogeneous Group of Stroke Patients.

Taguchi A, Sakai C, Soma T, Kasahara Y, Stern DM, Kajimoto K, Ihara M, Daimon T, Yamahara K, Doi K, Kohara N, Nishimura H, Matsuyama T, Naritomi H, Sakai N, Nagatsuka K - Stem Cells Dev. (2015)

Comparison between enrolled patients and historical controls at the time of discharge from the hospital. (a) Proportion of the patients with change for the worse in NIHSS score between day 7 after onset of stroke and discharge. (b, c) Significant improvement was observed in patients undergoing cell transplantation in NIHSS score (b, *P < 0.05) and improvement in NIHSS (day 7 after onset of stroke vs discharge) (c, *P < 0.05). (d–f) Although there was no statistical significant difference between groups in the level of mRS (d), ratio of favorable outcome (e), and Barthel Index (d), a trend toward improvement was observed in the cell therapy group in each case, compared with historical controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4582686&req=5

f6: Comparison between enrolled patients and historical controls at the time of discharge from the hospital. (a) Proportion of the patients with change for the worse in NIHSS score between day 7 after onset of stroke and discharge. (b, c) Significant improvement was observed in patients undergoing cell transplantation in NIHSS score (b, *P < 0.05) and improvement in NIHSS (day 7 after onset of stroke vs discharge) (c, *P < 0.05). (d–f) Although there was no statistical significant difference between groups in the level of mRS (d), ratio of favorable outcome (e), and Barthel Index (d), a trend toward improvement was observed in the cell therapy group in each case, compared with historical controls.
Mentions: Before initiation of this clinical trial, the medical records of 4,953 inpatients were surveyed and 539 cases were identified as acute cerebral embolism. Of the latter, 59 patients matched the entry criteria for our study to receive cell therapy. The mean age and NIHSS scores on days 0 and 7 after stroke were 66.7 ± 9.0, 18.5 ± 5.4, and 20.5 ± 8.3, respectively. The proportion of males was 37% (22/59). There was no significant difference in patient characteristics and outcomes between cell-treated and historical control groups, aside from gender (P < 0.05). Figure 6 shows the comparison of neurologic outcomes at the time of discharge, comparing patients who received cell therapy with historical controls. Although there was no significant difference in the proportion of change for the worse in NIHSS score between groups (Fig. 6a), a trend favoring improvement was observed in the group treated with bone marrow mononuclear cells. Thus, cell therapy did not increase the risk of worsening stroke outcome. Significant differences were observed between the two groups in NIHSS scores at the time discharge (Fig. 6b) (P < 0.05) and change of the NIHSS score between day 7 after onset of stroke and discharge (Fig. 6c) (P < 0.05). No statistical significance was observed in the mRS score (Fig. 6d), proportion of patients with the favorable outcome (Fig. 6e), and the Barthel Index score (Fig. 6f) between the two groups.

Bottom Line: Compared with 1 month after treatment, patients receiving cell therapy displayed a trend toward improved cerebral blood flow and metabolic rate of oxygen consumption 6 months after treatment.In comparison with historical controls, patients receiving cell therapy had significantly better neurologic outcomes.Our results indicated that intravenous transplantation of autologous bone marrow mononuclear cells is safe and feasible.

View Article: PubMed Central - PubMed

Affiliation: 1 Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation , Kobe, Japan .

ABSTRACT
The goal of this clinical trial was to assess the feasibility and safety of transplanting autologous bone marrow mononuclear cells into patients suffering severe embolic stroke. Major inclusion criteria included patients with cerebral embolism, age 20-75 years, National Institute of Health Stroke Scale (NIHSS) score displaying improvement of ≤ 5 points during the first 7 days after stroke, and NIHSS score of ≥ 10 on day 7 after stroke. Bone marrow aspiration (25 or 50 mL; N = 6 patients in each case) was performed 7-10 days poststroke, and bone marrow mononuclear cells were administrated intravenously. Mean total transplanted cell numbers were 2.5 × 10(8) and 3.4 × 10(8) cells in the lower and higher dose groups, respectively. No apparent adverse effects of administering bone marrow cells were observed. Compared with the lower dose, patients receiving the higher dose of bone marrow cells displayed a trend toward improved neurologic outcomes. Compared with 1 month after treatment, patients receiving cell therapy displayed a trend toward improved cerebral blood flow and metabolic rate of oxygen consumption 6 months after treatment. In comparison with historical controls, patients receiving cell therapy had significantly better neurologic outcomes. Our results indicated that intravenous transplantation of autologous bone marrow mononuclear cells is safe and feasible. Positive results and trends favoring neurologic recovery and improvement in cerebral blood flow and metabolism by cell therapy underscore the relevance of larger scale randomized controlled trials using this approach.

No MeSH data available.


Related in: MedlinePlus