Objective:
The application of autologous bone marrow cells has emerged as an investigational cell-based therapy for ischemic stroke. Previous animal studies have reported that stroke affects leukocytes in the bone marrow. In addition, older age and presence of comorbidities raise concerns about the variability in yield of bone marrow stem cells. These issues may potentially impact autologous applications of bone marrow cell therapies in stroke patients. We examined whether acute ischemic stroke (AIS) affects the bone marrow in patients by assessing various cell subpopulations within the mononuclear fraction of bone marrow harvested from healthy donors and study patients in our clinical trial testing mononuclear cells (MNCs) in patients with AIS.
Methods:
This study examined the bone marrow composition of 22 consecutive patients with AIS enrolled into our clinical trial testing the safety of autologous bone marrow MNCs administered intravenously within 24 to 72 hours after symptom onset. After bone marrow harvest, MNCs are isolated, separated, and characterized at a GMP facility. The bone marrow from 15 healthy donors was also processed at the same GMP facility. Descriptive analysis comprised calculation of means for absolute cell counts and determination of proportions for subtypes of different cell subpopulations. Samples of healthy bone marrow donors were compared with that of AIS patients.
Results:
AIS patients had a median age of 61 (IQR 50-73), had CAD (5%), Afib (14%), diabetes (32%), hypertension (50%), hyperlipidemia (32%), or were actively smoking (27%). Onset time to harvest was 48 ±11 hours after stroke onset.
Figure 1
shows no significant differences among the proportions of cell populations including lineage negative, CD34+ cells (a marker of hematopoietic stem cells - HSCs). There was no significant difference in the variance of the cell subpopulations between healthy donors and stroke patients, except for NK cells which were significantly higher among the stroke patients (p = 0.0074). Age, history of DM, or the location of the infarct depending on vascular territory did not affect the proportion of the different cell populations.
Conclusions:
AIS does not cause significant changes in the proportions of different cell types in the MNCs of bone marrow including the HSCs. We found no evidence that autologous MNCs are different, in terms of cell composition, from study patients who are older and have vascular comorbidities compared with healthy donors.
An exploratory randomized control study of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with ischaemic cardiomyopathy: the REGENERATE-IHD clinical trial
