Role of monocytes in regenerative cell therapies

by Alexey Bersenev on February 16, 2014 · 0 comments

in cord blood

As I’ve written before, we largely don’t know what cell population underlies the mechanism of action of bone marrow or cord blood transplantation in regenerative medicine. Before infusion in neurological, cardiac, hepatic and other conditions, cord blood or bone marrow usually undergo minimal processing – red blood cells and platelet depletion. What remains before infusion is so-called mononuclear fraction (MNC) – a mix of white blood cells. It would be too naive to assume that only stem cells from MNC will do all “therapeutic job”. In reality, we have no idea what the value of different MNC populations in therapeutic effects. Recent study shed some light on this puzzle. The authors demonstrated that cord blood monocytes are essential in neuroprotective effect in stroke model.

Multiple independent groups have demonstrated before, that human cord blood MNC can ameliorate neurological deficit in stroke model. Now researchers used an elegant strategy to figure out the therapeutic value of different cord blood MNC populations. Using magnetic sorting (MACS) strategy, they depleted monocytes (CD14+), T-cells (CD2+), B-cells (CD19+) or stem cells (CD133+) from human cord blood MNC fraction. Whole unfractioned MNC and all different MNC fractions were infused in rat stroke model. Infarct size and behavioral tests were performed before and after cell therapy. Results were the following:

Activity levels and infarct size of the animals treated with monocyte depleted HUCB MNC were similar to that observed in the untreated MCAO group. When animals were treated with enriched fractions of CD14 + cells infarct size decreased to the same extent as with the MNC treated group. These results suggest that HUCB monocytes are the critical cellular component of HUCB MNC fraction that induces recovery after MCAO.

The authors observed the same results when they used CD14+ monocytes, derived from peripheral blood. It means that therapeutic value of monocytes did not depend on cell source. Unfortunately, study does not provide conclusive data (because of MACS inefficiency) about value of T-cells and stem cells:

Our data in those animals that received the CD133 (stem cell) and CD2 (T cell) depleted HUCB preparations do not allow us to draw any firm conclusions about the role of these cells in HUCB induced recovery after MCAO since the MACS sorting only depleted 52.9% and 22.3% respectively of these cells from the MNC fraction.

This is not the first study, which highlights therapeutic value of monocytes. Two studies (Award 2006 and Sanchez-Guijo 2010) demonstrated that human blood CD14+ and mouse bone marrow CD11b+ cells improve angiogenesis in hind limb ischemia models, irrespective of administration route (i.v. or i.m.). In the cardiac clinical trial, improvement of heart function was linked to monocyte content in bone marrow-derived MNC, but not to lymphocytes or stem cells number. In all these cases, there were no evidence for cell integration, engraftment and persistence.

The results of this and other similar studies support my view on defining “stem cell therapy” in relation to mechanism of action. When we use MNC fraction (from peripheral blood, cord blood, bone marrow, adipose SVF) in regenerative medicine, we have now more evidence for therapeutic value of mature cells (such as monocytes) than for the stem cells.

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