scholarly journals Comparative Dose of Intracarotid Autologous Bone Marrow Mononuclear Therapy in Chronic Ischemic Stroke in Rats

2021 ◽  
Vol 9 (A) ◽  
pp. 233-243
Author(s):  
Feda Makkiyah ◽  
Wismaji Sadewo ◽  
Rahmah Nurrizka
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Ischemic Stroke ◽  
Test Scores ◽  
Mononuclear Cells ◽  
Marrow Cell ◽  
Optimum Dose ◽  
Infarct Zone ◽  
Positive Effects ◽  
Cylinder Test

Research on chronic ischemic stroke is limited. One of the more promising approaches showing positive effects in the acute stage is mononuclear bone marrow cell therapy. This research may be the first which presents data about the optimum dose of bone marrow mononuclear cells (BM-MNCs) for chronic ischemic stroke in rats and discusses factors influencing recovery in the chronic stage. We performed temporary middle cerebral artery occlusion (MCAO)  procedures on the rats which were then randomly assigned to one of two experimental groups in which they were given either low or high doses of autologous BM-MNCs  (5 million or 10 million cells per kg body weight). Rat brains were fixed for HE, CD31, and doublecortin staining for analysis of the effects. Rat behavior was assessed weekly using the cylinder test and a modified neurological severity score (NSS) test. In the four weeks prior to administration of BM-MNC, cylinder test scores improved to near normal, and NSS test scores improved moderately. The infarct zone decreased significantly (p <0,01),  there was an improvement in angiogenesis (p = 0.1590) and a significant improvement in neurogenesis (p <0,01). Reduction of the infarct zone was associated with a higher dose whereas both higher and lower doses were found to have a similar effect on improving angiogenesis, and neurogenesis. Recovery was superior after twelve weeks compared with the recovery assessment at eight weeks. In conclusion, a dose of 10 million cells was more effective than a dose of 5 million cells per kg body weight for reducing the infarct zone and ameliorating neurogenesis. There was an improvement of histopathological parameters associated with the longer infarct period.

scholarly journals Ischemic Stroke May Activate Bone Marrow Mononuclear Cells to Enhance Recovery After Stroke

2012 ◽  
Vol 21 (18) ◽  
pp. 3332-3340 ◽  
Author(s):  
Bing Yang ◽  
XiaoPei Xi ◽  
Jaroslaw Aronowski ◽  
Sean I. Savitz
Keyword(s):  
Bone Marrow ◽  
Ischemic Stroke ◽  
Mononuclear Cells ◽  
Bone Marrow Mononuclear Cells

Intravenous autologous bone marrow mononuclear cells for ischemic stroke

2011 ◽  
Vol 70 (1) ◽  
pp. 59-69 ◽  
Author(s):  
Sean I. Savitz ◽  
Vivek Misra ◽  
Mallik Kasam ◽  
Harrinder Juneja ◽  
Charles S. Cox ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ischemic Stroke ◽  
Mononuclear Cells ◽  
Autologous Bone Marrow ◽  
Bone Marrow Mononuclear Cells ◽  
Autologous Bone

scholarly journals Stimulation of nonclonal hematopoiesis and suppression of the neoplastic clone after treatment with recombinant human granulocyte- macrophage colony-stimulating factor in a patient with therapy-related myelodysplastic syndrome

Blood ◽  
1989 ◽  
Vol 74 (5) ◽  
pp. 1491-1498 ◽  
Author(s):  
S Vadhan-Raj ◽  
HE Broxmeyer ◽  
G Spitzer ◽  
A LeMaistre ◽  
S Hultman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mononuclear Cells ◽  
Fragment Length Polymorphism ◽  
Marrow Cell ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Selective Growth Advantage ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract A complete hematologic remission was achieved in a patient with therapy- related preleukemia and transfusion-dependent pancytopenia after treatment with recombinant human granulocyte-macrophage colony- stimulating factor (GM-CSF). The patient remained in remission for nearly 1 year despite the discontinuation of GM-CSF treatment. Several lines of evidence suggest that normal hematopoiesis was restored after GM-CSF treatment. First, the cytogenetic anomaly, which was present before GM-CSF, completely disappeared after three cycles of treatment. Cytogenetic conversion was documented by conventional karyotypic evaluation of mitotic bone marrow cell preparations as well as by premature chromosome condensation analysis of the nonmitotic cells of bone marrow and peripheral blood. Second, the growth pattern and cycle status of bone marrow granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells were found to be normal during remission. Third, X chromosome-linked restriction fragment length polymorphism- methylation analysis of DNA from mononuclear cells (greater than 80% lymphocytes) and mature myeloid elements showed a polyclonal pattern. These findings suggest that restoration of hematopoiesis in this patient after GM-CSF treatment may have resulted from suppression of the abnormal clone and a selective growth advantage of normal elements.

scholarly journals Intravenous Bone Marrow Mononuclear Cells for Acute Ischemic Stroke: Safety, Feasibility, and Effect Size from a Phase I Clinical Trial

Stem Cells ◽  
2019 ◽  
Vol 37 (11) ◽  
pp. 1481-1491 ◽  
Author(s):  
Farhaan S. Vahidy ◽  
Muhammad E. Haque ◽  
Mohammad H. Rahbar ◽  
Hongjian Zhu ◽  
Paul Rowan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Ischemic Stroke ◽  
Phase I ◽  
Acute Ischemic Stroke ◽  
Effect Size ◽  
Mononuclear Cells ◽  
Phase I Clinical Trial ◽  
Bone Marrow Mononuclear Cells

scholarly journals Systematic Review and Meta-Analysis of Bone Marrow–Derived Mononuclear Cells in Animal Models of Ischemic Stroke

Stroke ◽  
2016 ◽  
Vol 47 (6) ◽  
pp. 1632-1639 ◽  
Author(s):  
Farhaan S. Vahidy ◽  
Mohammad H. Rahbar ◽  
Hongjian Zhu ◽  
Paul J. Rowan ◽  
Arvind B. Bambhroliya ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bone Marrow ◽  
Ischemic Stroke ◽  
Animal Models ◽  
Mononuclear Cells ◽  
Meta Analysis

scholarly journals Stimulation of nonclonal hematopoiesis and suppression of the neoplastic clone after treatment with recombinant human granulocyte- macrophage colony-stimulating factor in a patient with therapy-related myelodysplastic syndrome

Blood ◽  
1989 ◽  
Vol 74 (5) ◽  
pp. 1491-1498 ◽  
Author(s):  
S Vadhan-Raj ◽  
HE Broxmeyer ◽  
G Spitzer ◽  
A LeMaistre ◽  
S Hultman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mononuclear Cells ◽  
Fragment Length Polymorphism ◽  
Marrow Cell ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Selective Growth Advantage ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

A complete hematologic remission was achieved in a patient with therapy- related preleukemia and transfusion-dependent pancytopenia after treatment with recombinant human granulocyte-macrophage colony- stimulating factor (GM-CSF). The patient remained in remission for nearly 1 year despite the discontinuation of GM-CSF treatment. Several lines of evidence suggest that normal hematopoiesis was restored after GM-CSF treatment. First, the cytogenetic anomaly, which was present before GM-CSF, completely disappeared after three cycles of treatment. Cytogenetic conversion was documented by conventional karyotypic evaluation of mitotic bone marrow cell preparations as well as by premature chromosome condensation analysis of the nonmitotic cells of bone marrow and peripheral blood. Second, the growth pattern and cycle status of bone marrow granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells were found to be normal during remission. Third, X chromosome-linked restriction fragment length polymorphism- methylation analysis of DNA from mononuclear cells (greater than 80% lymphocytes) and mature myeloid elements showed a polyclonal pattern. These findings suggest that restoration of hematopoiesis in this patient after GM-CSF treatment may have resulted from suppression of the abnormal clone and a selective growth advantage of normal elements.

Abstract 15627: Identification of Cardiovascular Risk Factors Associated With Bone Marrow Cell Subsets in Patients With STEMI: A Biorepository Evaluation From the CCTRN TIME and LateTIME Clinical Trials

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ariadna Contreras ◽  
Aaron F Orozco ◽  
Robert C Schutt ◽  
Micheline M Resende ◽  
Luiz Sampaio ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Cardiovascular Risk ◽  
Cell Therapy ◽  
Cardiovascular Risk Factors ◽  
Mononuclear Cells ◽  
Marrow Cell ◽  
Flow Cytometric Analysis ◽  
Autologous Bone Marrow ◽  
St Segment Elevation

Objective: Results from several randomized, controlled cell therapy trials suggest that the use of autologous bone marrow mononuclear cells (BMMNCs) results in only modest benefits in patients with ST-segment elevation myocardial infarction (STEMI). However, the patients in these trials had varying combinations of underlying cardiovascular risk factors (CVRFs) and comorbidities. The autologous BMMNC product administered to each patient was unique. Based on our previous findings, the purpose of this study was to identify potential associations between specific CVRFs and BMMNC subsets in patients with STEMI. Methods: This study evaluated a cohort of patients with STEMI who were enrolled in either the CCTRN TIME or LateTIME trials and underwent BMMNC or placebo treatment (N=139). Flow cytometric analysis targeting phenotypic markers (eg, CD45, CD14, CD11b, CD3, CD19, CD31, and CD34) was used to assess the frequency of BMMNC subsets at baseline. The GRACE ACS Risk Score 2.0 - 3 year death (GRS) was used to stratify patients according to cardiovascular risk (low: GRS <12%, moderate: GRS 12-30%, high: GRS >30%). Multivariable models were then applied to assess relationships between BMMNC subsets and CVRFs, including age, smoking, hypertension, hyperlipidemia, and sex. Results: Patients were grouped as low GRS (n=69, 49.6%), moderate GRS (n=49, 35.3%), and high GRS (n=21, 15.1%). Patients with a high GRS had significantly lower frequencies of CD45+CD31+ cells than those with a low GRS (35.6% vs 40.3%, respectively, P=0.041). In multivariable analyses, age was inversely associated with the frequencies of CD34+ (P=0.011) and CD45+CD31+ (P=0.001) cells, and smoking was associated with a decrease in CD45+CD31+ cells (P=0.022). In addition, higher frequencies of CD11b+ cells were associated with hypertension (P=0.010) and hyperlipidemia (P=0.029). In contrast, the CD11b+ cell frequency was less in females (P=0.005). Conclusions: This study identified associations between specific CVRFs and BMMNC subsets. These associations may contribute to the heterogeneity of the cell product received. Thus, differences in patients’ comorbidities should be considered when designing future autologous cell therapy trials.

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