Human umbilical cord blood monocytes, but not adult blood monocytes, rescue brain cells from hypoxic-ischemic injury: Mechanistic and therapeutic implications.


Cord blood (CB) mononuclear cells (MNC) are being tested in clinical trials to treat hypoxic-ischemic (HI) brain injuries. Although early results are encouraging, mechanisms underlying potential clinical benefits are not well understood. To explore these mechanisms further, we exposed mouse brain organotypic slice cultures to oxygen and glucose deprivation (OGD) and then treated the brain slices with cells from CB or adult peripheral blood (PB). We found that CB-MNCs protect neurons from OGD-induced death and reduced both microglial and astrocyte activation. PB-MNC failed to affect either outcome. The protective activities were largely mediated by factors secreted by CB-MNC, as direct cell-to-cell contact between the injured brain slices and CB cells was not essential. To determine if a specific subpopulation of CB-MNC are responsible for these protective activities, we depleted CB-MNC of various cell types and found that only removal of CB CD14+ monocytes abolished neuroprotection. We also used positively selected subpopulations of CB-MNC and PB-MNC in this assay and demonstrated that purified CB-CD14+ cells, but not CB-PB CD14+ cells, efficiently protected neuronal cells from death and reduced glial activation following OGD. Gene expression microarray analysis demonstrated that compared to PB-CD14+ monocytes, CB-CD14+ monocytes over-expressed several secreted proteins with potential to protect neurons. Differential expression of five candidate effector molecules, chitinase 3-like protein-1, inhibin-A, interleukin-10, matrix metalloproteinase-9 and thrombospondin-1, were confirmed by western blotting, and immunofluorescence. These findings suggest that CD14+ monocytes are a critical cell-type when treating HI with CB-MNC.





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Publication Info

Saha, Arjun, Sachit Patel, Li Xu, Paula Scotland, Jonathan Schwartzman, Anthony J Filiano, Joanne Kurtzberg, Andrew E Balber, et al. (2019). Human umbilical cord blood monocytes, but not adult blood monocytes, rescue brain cells from hypoxic-ischemic injury: Mechanistic and therapeutic implications. PloS one, 14(9). p. e0218906. 10.1371/journal.pone.0218906 Retrieved from

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Anthony J Filiano

Assistant Professor in Neurosurgery

Immune dysfunction has been described in most neurological disorders. Preclinical strategies targeting these disorders have primarily concentrated on directly targeting synaptic function; however, most of these approaches have failed. Our lab is interested in understanding the complex interactions between the immune system and nervous system with the intent to uncover novel therapeutic targets to combat diseases such as autism spectrum disorder.

 Projects in the Lab:

  1. T cells support proper brain function and mice lacking T cells have behavioral deficits, such as decreased learning and memory and social withdrawal. Further, alterations in T cell function have been described in many neurological disorders. Interestingly, T cells are not present in the parenchyma of a healthy brain; yet they patrol the meninges and likely influence neuronal activity via the release of soluble cytokines. We are investigating how cytokines, and other immune-cell derived molecules, can regulate neural circuits and how an imbalance in these molecules might affect the brain in autism spectrum and other related disorders.               
  2. Cord blood contains a rich source of immune-modulating components including, stem cells, immune cells, and soluble factors. Recent work has demonstrated the efficacy of using cord-blood derived components to promote myelination and increase function in neurological conditions such as multiple sclerosis, autism spectrum disorder, and aging. We are investigating how cord-blood derived cells and products can be used to promote healthy brain function and alleviate behavioral dysfunction in these devastating neurological conditions.


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