Autologous Bone Marrow Mononuclear Cells in Ischemic Cerebrovascular Accident Paves Way for Neurorestoration: A Case Report

In response to acute ischemic stroke, large numbers of bone marrow stem cells mobilize spontaneously in peripheral blood that home onto the site of ischemia activating the penumbra. But with chronicity, the numbers of mobilized cells decrease, reducing the degree and rate of recovery. Cellular therapy has been explored as a new avenue to restore the repair process in the chronic stage. A 67-year-old Indian male with a chronic right middle cerebral artery ischemic stroke had residual left hemiparesis despite standard management. Recovery was slow and partial resulting in dependence to carry out activities of daily living. Our aim was to enhance the speed of recovery process by providing an increased number of stem cells to the site of injury. We administered autologous bone marrow mononuclear cells intrathecally alongwith rehabilitation and regular follow up. The striking fact was that the hand functions, which are the most challenging deficits, showed significant recovery. Functional Independence Measure scores and quality of life improved. This could be attributed to the neural tissue restoration. We hypothesize that cell therapy may be safe, novel and appealing treatment for chronic ischemic stroke. Further controlled trials are indicated to advance the concept of Neurorestoration.

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Intravenous autologous bone marrow mononuclear cells for ischemic stroke

Annals of Neurology ◽

10.1002/ana.22458 ◽

2011 ◽

Vol 70 (1) ◽

pp. 59-69 ◽

Cited By ~ 186

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

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A Randomized Comparative Study on the Efficacy of Intracoronary Infusion of Autologous Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells in Patients With Dilated Cardiomyopathy

International Heart Journal ◽

10.1536/ihj.16-328 ◽

2017 ◽

Vol 58 (2) ◽

pp. 238-244 ◽

Cited By ~ 21

Author(s):

Wentao Xiao ◽

Suping Guo ◽

Chuanyu Gao ◽

Guoyou Dai ◽

Yongjv Gao ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Comparative Study ◽

Dilated Cardiomyopathy ◽

Mononuclear Cells ◽

Autologous Bone Marrow ◽

Bone Marrow Mononuclear Cells ◽

Intracoronary Infusion ◽

Autologous Bone

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Autologous Bone Marrow Mononuclear Cells Enhance Recovery after Acute Ischemic Stroke in Young and Middle-Aged Rats

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2009.198 ◽

2009 ◽

Vol 30 (1) ◽

pp. 140-149 ◽

Cited By ~ 137

Author(s):

Miranda Brenneman ◽

Sushil Sharma ◽

Matthew Harting ◽

Roger Strong ◽

Charles S Cox ◽

...

Keyword(s):

Bone Marrow ◽

Ischemic Stroke ◽

Carotid Artery ◽

Acute Ischemic Stroke ◽

Mononuclear Cells ◽

Infarct Volume ◽

Autologous Bone Marrow ◽

Needle Insertion ◽

Bone Marrow Mononuclear Cells ◽

Autologous Bone

We investigated intra-arterially administered autologous bone marrow mononuclear cells (MNCs) in rats with acute ischemic stroke. Long Evans rats (2 to 3 months or 12 months old) underwent tandem reversible common carotid artery (CCA)/middle cerebral artery (MCA) occlusion (CCAo/MCAo) for 3 h and then 24 h later underwent tibial bone marrow harvest. Ten million or 4 million cells were re-injected by an intra-carotid infusion. Control animals underwent marrow needle insertion and then saline injection into the carotid artery. Animals were assessed on a battery of neurological tests. MNCs in the ischemic brain were tracked using Q-dot nanocrystal labeling. Infarct volume and cytokines in the ischemia-affected brain were analyzed. Cell-treated animals in the younger and older groups showed improvement from 7 to 30 days after stroke compared with vehicle-treated animals. MNCs significantly reduced infarct volume compared with saline. There was a significant reduction in tumor necrosis factor-α, interleukin-1α (IL-1α), IL-β, IL-6, and a significant increase in IL-10 in injured brains harvested from the cell-treated groups compared with saline controls. Labeled MNCs were found in the peri-infarcted area at 1 h and exponentially decreased over the ensuing week after injection. Autologous bone marrow MNCs can be safely harvested from rodents after stroke, migrate to the peri-infarct area, enhance recovery, and modulate the post-ischemic inflammatory response.

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Characterization of Mesenchymal Stem Cells of “No-Options” Patients with Critical Limb Ischemia Treated by Autologous Bone Marrow Mononuclear Cells

PLoS ONE ◽

10.1371/journal.pone.0073722 ◽

2013 ◽

Vol 8 (9) ◽

pp. e73722 ◽

Cited By ~ 27

Author(s):

Cestmir Altaner ◽

Veronika Altanerova ◽

Marina Cihova ◽

Lubica Hunakova ◽

Katarina Kaiserova ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Critical Limb Ischemia ◽

Mononuclear Cells ◽

Autologous Bone Marrow ◽

Limb Ischemia ◽

Bone Marrow Mononuclear Cells ◽

Autologous Bone

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Abstract 118: Intravenous versus Intra-arterial Autologous Bone Marrow Mononuclear cells for Acute Ischemic Stroke

Stroke ◽

10.1161/str.43.suppl_1.a118 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Bing Yang ◽

Ramy El Khoury ◽

Krystal Schaar ◽

Xiaopei Xi ◽

Sean.I Savitz

Keyword(s):

Bone Marrow ◽

Clinical Trials ◽

Ischemic Stroke ◽

Mononuclear Cells ◽

Autologous Bone Marrow ◽

Serum Levels ◽

Bone Marrow Mononuclear Cells ◽

Stroke Model ◽

Tnf Α ◽

Autologous Bone

Background: Bone marrow mononuclear cells (MNCs) are under investigation as an autologous cell-based therapy for acute ischemic stroke. Both intravenous (IV) and intra-arterial (IA) delivery of MNCs have been brought forward to clinical trials. However, the optimal route of administration for these cells is still unknown and debated. In the present study, we performed a direct comparison of IV vs IA administration of MNCs in a rodent stroke model. Methods: Long Evans adult male rats were subjected to middle cerebral artery occlusion (MCAo) for 90 minutes. At 24 hrs after stroke, animals were randomly assigned to either receive saline IV (N=5) or autologous bone marrow derived MNCs 30 million cells/kg via IV (N= 9) injection or an IA (N=8) administration of autologous MNCs 30 million cells/kg. IA infusion was performed over 5 minutes with an infusion pump. Contralateral forepaw use was evaluated by an investigator blinded to treatment groups up to 28 days after stroke. Stroke lesion volume was also measured at 28 days after stroke. Serum cytokines were analyzed from 4 to 28 days after stroke. Results: MNCs improved functional recovery and reduced lesion size compared with saline treatment at 28 days after stroke ( Fig A & Fig B, p<0.05). However, there was no significant difference between IV and IA MNC treated groups in either histological or functional outcomes. Serum levels of IL-10 were elevated in animals that received either IV or IA MNCs from 4 to 28 days after stroke, compared with saline controls (Fig C, p<0.05). In addition, serum levels of TNF-α were significantly reduced (Fig D, p<0.05) in both IV and IA MNC treated groups compared to saline controls. We did not observe differences in cytokine levels between IA and IV MNC treated groups for IL-10 and TNF-α. Furthermore, only intravenously administered MNCs led to a significant reduction in serum IL-1β levels, at 4 days after stroke, compared to saline treated controls (p<0.05). Conclusion: This is the first study to directly compare delivery routes of bone marrow derived MNCs in a rodent stroke model and assess long term outcomes. MNCs improved neurological recovery and reduced infarction sizes after stroke but we found no differences in outcome based on route of administration. We also found no evidence that either delivery route is superior in modulating the systemic inflammatory response after stroke. These findings have direct clinical implications for the design of clinical trials testing MNCs in patients with ischemic stroke.

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Treatment of Chronic Patellar Tendinopathy with Autologous Bone Marrow Stem Cells: A 5-Year-Followup

Stem Cells International ◽

10.1155/2012/953510 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 58

Author(s):

Cecilia Pascual-Garrido ◽

A. Rolón ◽

A. Makino

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mononuclear Cells ◽

Autologous Bone Marrow ◽

Patellar Tendinopathy ◽

Bone Marrow Mononuclear Cells ◽

Ultrasound Guide ◽

Clinical Scores ◽

Tendon Lesion ◽

Autologous Bone

The purpose of this study is to determine if patients with chronic patellar tendinopathy will improve clinically after the inoculation of bone marrow mononuclear cells (BM-MNCs). Eight patients with chronic patellar tendinopathy were included. Patients averaged 24 years old (range 14–35). All patients were refractory to conservative treatment for at least 6 months before the procedure. BM-MNCs were harvested from the iliac bone crest and inoculated under ultrasound guide in the patellar tendon lesion. Improvement was assessed through established clinical scores and ultrasound. At 5-year followup, statistically significant improvement was seen for most clinical scores. Seven of eight patients said they would have the procedure again if they had the same problem in the opposite knee and were completely satisfied with the procedure. Seven of 8 patients thought that the results of the procedure were excellent. According to our results, inoculation of BM-MNCs could be considered as a potential therapy for those patients with chronic patellar tendinopathy refractory to nonoperative treatments.

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Intra-Arterial Infusion of Autologous Bone-Marrow Mononuclear Cells in Patients with Moderate to Severe Middle-Cerebral-Artery Acute Ischemic Stroke

Cell Transplantation ◽

10.3727/096368911x612512 ◽

2012 ◽

Cited By ~ 1

Author(s):

Maurício Friedrich

Keyword(s):

Bone Marrow ◽

Ischemic Stroke ◽

Middle Cerebral Artery ◽

Acute Ischemic Stroke ◽

Cerebral Artery ◽

Mononuclear Cells ◽

Autologous Bone Marrow ◽

Bone Marrow Mononuclear Cells ◽

Arterial Infusion ◽

Autologous Bone

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A Clinical Study of Autologous Bone Marrow Mononuclear Cells for Cerebral Palsy Patients: A New Frontier

Stem Cells International ◽

10.1155/2015/905874 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 21

Author(s):

Alok Sharma ◽

Hemangi Sane ◽

Nandini Gokulchandran ◽

Pooja Kulkarni ◽

Sushant Gandhi ◽

...

Keyword(s):

Bone Marrow ◽

Cerebral Palsy ◽

Mononuclear Cells ◽

Cellular Therapy ◽

Autologous Bone Marrow ◽

Bone Marrow Mononuclear Cells ◽

Open Label ◽

Pet Ct ◽

Study Population ◽

Autologous Bone

Cerebral palsy is a nonprogressive heterogeneous group of neurological disorders with a growing rate of prevalence. Recently, cellular therapy is emerging as a potential novel treatment strategy for cerebral palsy. The various mechanisms by which cellular therapy works include neuroprotection, immunomodulation, neurorestoration, and neurogenesis. We conducted an open label, nonrandomized study on 40 cases of cerebral palsy with an aim of evaluating the benefit of cellular therapy in combination with rehabilitation. These cases were administered autologous bone marrow mononuclear cells intrathecally. The follow-up was carried out at 1 week, 3 months, and 6 months after the intervention. Adverse events of the treatment were also monitored in this duration. Overall, at six months, 95% of patients showed improvements. The study population was further divided into diplegic, quadriplegic, and miscellaneous group of cerebral palsy. On statistical analysis, a significant association was established between the symptomatic improvements and cell therapy in diplegic and quadriplegic cerebral palsy. PET-CT scan done in 6 patients showed metabolic improvements in areas of the brain correlating to clinical improvements. The results of this study demonstrate that cellular therapy may accelerate the development, reduce disability, and improve the quality of life of patients with cerebral palsy.

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