Monocyte transplantation for neural and cardiovascular ischemia repair

Abstract

Neovascularization is an integral process of inflammatory reactions and subsequent repair cascades in tissue injury. Monocytes/macrophages play a key role in the inflammatory process including angiogenesis as well as the defence mechanisms by exerting microbicidal and immunomodulatory activity. Current studies have demonstrated that recruited monocytes/macrophages aid in regulating angiogenesis in ischemic tissue, tumours and chronic inflammation. In terms of neovascularization followed by tissue regeneration, monocytes/macrophages should be highly attractive for cell-based therapy compared to any other stem cells due to their considerable advantages: non-oncogenic, non-teratogenic, multiple secretary functions including pro-angiogenic and growth factors, straightforward cell harvesting procedure and non-existent ethical controversy. In addition to adult origins such as bone marrow or peripheral blood, umbilical cord blood (UCB) can be a potential source for autologous or allogeneic monocytes/macrophages. Especially, UCB monocytes should be considered as the first candidate owing to their feasibility, low immune rejection and multiple characteristic advantages such as their anti-inflammatory properties by virtue of their unique immune and inflammatory immaturity, and their pro-angiogenic ability. In this review, we present general characteristics and potential of monocytes/macrophages for cell-based therapy, especially focusing on neovascularization and UCB-derived monocytes.

Fig 1

Schematic diagram depicting monocyte/macrophage ontogeny. The pluripotent stem cells differentiate into myeloid or lymphoid progenitors in BM. The granulocyte–monocyte progenitors are derived from the common myeloid progenitor cell before differentiating into myeloblast and monoblast. Monocytes are differentiated from monoblast and subsequently move from the BM into the blood. Blood monocytes differentiate into various types of resident macrophages depending on their anatomical locations after extravasating into tissues. On the other hand, during the early inflammatory process, recruitment and transendothelial migration of circulating monocytes is augmented by a series of adhesion and chemotactic materials, expressed by inflammatory cells. Recruited monocytes migrate along chemotactic and oxygen gradients between normal and injured tissues, and accumulate within inflammatory and hypoxic cores in ischemia, or solid tumours, or chronic inflammatory diseases before differentiation into recruited macrophages which have polarization, M1 or M2 subset.

Fig 2

Neuroprotection of striatal and cortical degeneration after middle cerebral artery occlusion in a rat model of stroke is attenuated by removal of monocytes. There is extensive neurodegeneration in striatum and cortex after middle cerebral artery occlusion as determined with FluoroJade staining (top panel). Administering human UCB cells minimizes this damage (bottom panel) whereas removal of the CD14⁺ monocytes from the human UCB eliminates this neuroprotective effect. Scale bar = 2.0 mm. (From Womble et al.[102].)