**5. Mesenchymal stem cell phagocytosis**

Mesenchymal stem cells (MSCs) are multipotent cells capable of regeneration and differentiation into multiple cell types [147]. They reside in a wide number of tissues and give rise to cells and tissues necessary for growth, development, and tissue repair. MSCs

are frequently referred to as adult stem cells, along with hematopoietic stem cells (HSCs), which of course give rise to professional phagocytes. Adult stem cells, such as MSCs, are multipotent and distinguished from embryonic stem cells (ESCs) or laboratorygenerated induced pluripotent stem cells (iPSCs), which are pluripotent with a differentiation capacity to generate cells of all three germ layers. MSCs are stromal cells, and distinct from their HSC counterparts, it is therefore perhaps surprising that an advanced cellular function such as phagocytosis has been observed. Several reports, however, have demonstrated that MSCs are indeed capable of phagocytosis. This was first reported in 2000 by Wood *et. al*, who demonstrated the ability of mesenchymal cells to clear apoptotic cells through efferocytosis in the absence of macrophages in PU.1 knock-out mice [11] and later established in 2010 when Tso *et. al* confirmed efferocytosis-like clearance of apoptotic cells by MSCs [10]. Since then, other reports have corroborated this finding in a variety of situations, confirming MSCs capabilities of efferocytosis and clearance of apoptotic cells [12, 148]. What is also surprising is the inflammatory response when apoptotic bodies are recognized by mesenchymal cells, including NF-κB signaling pathway activation [12], and MSCs can express a number of distinctive markers more closely associated with immune cells [149]. Furthermore, MSCs are capable of secreting antimicrobial peptides [150, 151] to aid in pathogen killing and clearance.

MSCs do possess a certain level of PRRs, including TLRs [152] and NOD-like receptors [153]; however, reports are lacking that definitively demonstrate exogenous pathogen phagocytosis although have suggested its plausibility [154]. Similar to endothelial cells, MSCs are capable of MHC-II type antigen presentation [155], considered to be unique to professional phagocytes, and these antigen-presenting MSCs are capable of presenting and activating T cells [156, 157]. This would suggest that phagocytosis of pathogens, to present antigens *via* MHC-II is possible; however, this has yet to be confirmed. The primary function is therefore that of a supporting role for professional phagocytes as opposed to being primary phagocytes themselves.
