The Sca1+ mesenchymal stromal subpopulation promotesdendritic cell commitment in the niche

Abstract

IntroductionDendritic cells (DCs) are essential mediators in innate and adaptive immune responses. Except for Langerhans cells, DCs are derived from hematopoietic stem cells (HSCs) (Belz and Nutt, 2012;Satpathy et al., 2012;Seillet and Belz, 2013). Evidence has shown that self-renewing or the differentiation of HSCs, including DC commitment, mainly occurs in the bone marrow, with a high probability of being regulated by the hematopoietic microenvironment (niche) (Schraml et al., 2013). However, little is known about how the endosteal niche regulates the development of DC progenitors in bone marrow. Mesenchymal stromal cells (MSCs) are the most important components in the niche (Frenette et al., 2013). Recently, Jiang et al. (2005) reported that MSCs inhibited DC differentiation and maturation (Spaggiari et al., 2009;Zhang et al., 2009;Lai et al., 2010), as well as DC effector properties, including antigen processing and presentation to T cells (Chiesa et al., 2011).MSCs are actually heterogenic mixtures. A recent study reported that different subpopulations of MSCs served as unclassical niche components in bone marrow, such as CXCL12-abundant reticular (CAR) cells (Sugiyama et al., 2006;Ding and Morrison, 2013), nestin + cells (Mendez-Ferrer et al., 2010), Mx-cre + cells (Park et al., 2012), leptin + receptor-expressing mesenchymal cells (Ding et al., 2012), adipocytes (Naveiras et al., 2009), CD146 + cells, CD166 + cells (Hudson et al., 2011), and CD271 + cells (Mabuchi et al., 2013). Sca1 is one of the MSC markers (Morikawa et al., 2009). Many markers were used to identify in situ and/ or to isolate MSCs in mice, such as CD29, CD51, CD73, CD90, CD105, CD106, CD135, C-KIT, nestin, PDGFRα, and Sca1, but the lack of specific markers impedes identification of MSC functions (Galderisi and Giordano, 2014). Previously we enzymatically dissociated bone and separated the Sca1 + MSCs from the MSC mixture. Previously we also checked the purity of Sca1 + MSCs after isolation. Sca1 + MSCs were more than 80%, while CD45 + ,

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“…Studies examining heterogeneity in MSCs have identified multiple subpopulations of MSCs with varied potency for both differentiation and immunomodulation ( 35 – 40 ). Heterogeneous populations of MSC-like cells have been isolated from both adult and neonatal sources [e.g.…”

Identification of CD317-Positive Pro-inflammatory Immune Stromal Cells in Human Mesenchymal Stromal Cell Preparations

“…Studies examining heterogeneity in MSCs have identified multiple subpopulations of MSCs with varied potency for both differentiation and immunomodulation [35][36][37][38][39][40] . Heterogeneous populations of MSC-like cells have been isolated from both adult and neonatal sources (e.g.…”