Bone marrow-derived mononuclear cell populations in pediatric and adult patients
Introduction
There are more than 50 ongoing clinical trials evaluating ‘stem cells’ as a therapeutic intervention (www.clinicaltrials.gov). Among these studies, one of the most common specific cellular populations used is autologous mononuclear cells (MNC) derived from bone marrow (BM). The MNC fraction is a subset of cells that can be isolated rapidly from the BM and are known to be a source of stem and progenitor cells.
There are a number of advantages to using MNC for cell-therapy studies. MNC are easily and rapidly accessible, in adequate numbers, through a minimally invasive BM harvest, with minimal risk. Isolation and processing time from harvest to treatment is less than 6 h. Additionally, the availability of autologous cells avoids the risk of cell rejection, graft versus host disease (GvHD) and blood-borne disease transfer.
Concerns have been raised regarding MNC and progenitor cell yield that have been postulated to be inversely proportional to age in rodent 1., 2., 3. and human studies 4., 5., 6.. In specific niches, the number of germ line stem cells, their mitotic activity and the quantity of progeny generated all decline with age [7, 8]. Alternatively, both rodent [9] and human [10, 11] studies have also shown that MNC and mesenchymal stromal cell (MSC) numbers may not vary with age. Further, conflicting evidence indicates that specific cell properties, such as proliferative capacity and differentiation potential, may or may not be age dependent [1, 11].
Given the perceived differences in BM of growing pediatric patients and full-grown adults, comparison of younger patients with adults may offer insight into the phenotypic/functional characteristics. Our objective was therefore to compare the characterizations of BM and MNC populations derived from pediatric and adult patients. We analyzed BM-derived cells of pediatric and adult patients without cancer who were enrolled in clinical trial protocols testing the safety and efficacy of autologous MNC intervention. Cell number, viability, immunophenotype and initial proliferation potential were assessed and compared.
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Study population
Thirty-six patients (n=10 pediatric, n=26 adult) were included in this study. They had been enrolled in one of two study protocols: (1) safety of autologous MNC treatment in children with traumatic brain injury (pediatric group; n=10) or (2) safety of autologous MNC treatment in adults with cardiac disorders (adult group; n=26). Patient details are shown in Table I.
BM harvest/processing
BM aspiration from the posterior iliac crest was performed under aseptic conditions, with sedation and local anesthesia, by an
Patient population
The average age of the pediatric patients (n=10) was 8.8 ± 0.9 years (range 6.1–14.8 years) and the average age of the adult patients (n=26) was 58.5 ± 1.4 years (range 40–69 years). Average patient weights were 31.9 ± 4.1 kg (pediatric group) and 96.4 ± 2.6 kg (adult group).
BM and MNC counts
An average of 2.4 × 109 nucleated cells was harvested from the BM of the pediatric population and 1.5 × 109 nucleated cells from the BM of the adult population. After cellular separation, there were on average 2.1 × 106
Discussion
Identification of potential differences between BM-derived cell populations based on patient age is imperative, as promising pre-clinical data are translated to clinical trials involving patients of all ages. The potential efficacy of cell therapy may rely upon the properties or characteristics of the cells under investigation. MNC are one of the most commonly studied cell populations in cellular intervention clinical trials (www.clinicaltrials.gov), yet the mechanism of action of these cells
Acknowledgements
Sean I. Savitz was supported by a Howard Hughes Medical Institute award.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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