Epigenetic and in vivo comparison of diverse MSC sources reveals an endochondral signature for human hematopoietic niche formation

Abstract

Key Points Epigenetics and in vivo behavior can distinguish MSCs from different sources. BM-derived MSCs form a hematopoietic niche via a vascularized cartilage intermediate.

Cell therapy for bone fracture repair: A comparative preclinical review of mesenchymal stromal cells from bone marrow and from adipose tissue

“…Similarly, Noël et al [81] showed by microarray from Passage 1 (P1) BM-MSC and Ad-MSC that genes involved in chondro/osteogenesis, such as HES1, DLX5, TWIST1, BGLAP, OSX, SOX9, WNT5A, TGFΒ1 and VEGF were upregulated in BM-MSC. These results were confirmed recently in Reinisch et al [47] , which showed that genes related to chondro/osteogenesis such as RUNX2, RUNX3, BGLAP, MMP13, ITGA10, DLX5, DLX6, SPP1, BGLAP, ALPL, SPP1, COL2A, COL10A, and ACAN were upregulated in BM-MSC compared to Ad-MSC. The same researchers also confirmed that hemato/angiogenic genes such as INHBA, FZD1, TLR4, DGFC, ANGPT1, VEGFA, CTGF, and VEGFC were also upregulated in BM-MSC, confirming Brocher's results [42,47] .…”

“…The analysis of this literature underlines considerable variations between results obtained from different research teams that may be linked to the heterogeneity in (i) donors and donors' characteristics (e.g., health status, gender, age), (ii) in vitro/ex vivo protocols (e.g., sample isolation sites and methods, [33][34][35][36][37][38] , which represents the most robust comparison as they are not biased by inter-individual variabilities, in particular age, gender and health status. Nine studies comparing age-matched donors were also retained, which include 1 study on female donors only [39] , 1 study on 50% male and 50% female donors [40] , 2 studies on a close but not identical number of females and males [41,42] , and 5 studies on donors matched for age but without specifying the gender [43][44][45][46][47] . Finally, 4 studies compared the two types of MSC isolated from healthy donors, but with unknown age and gender [48][49][50][51] .…”

“…Therefore, only 4 papers were kept for this review. In these articles, BM-and Ad-MSC were expanded with a known and limited number of passages (P1 to P3), were grown in minimal conditions without induction towards lineage and were directly compared [39,42,47,81] .…”

“…According to the selection criteria of this review (i.e., age and gender matching donors), 6 articles have been selected [39,[42][43][44]47,81] . From these 6 publications however, 2 were discarded because the number of cell passages was either too large or not clearly specified [43] (using P2 to P6 cells without additional clarification), which can cause artefactual background, or because the comparison was not performed with non-induced BM-MSC and Ad-MSC (comparing only differentiated cells) [44] .…”

How One Thing Led to Another

“…Charles Chan has led our group in finding the mouse skeletal stem cell (SSC) that not only selfrenews but also gives rise at the single-cell level to osteocytes, chondrocytes, and up to four distinct marrow stromal cells (124). Placed under the kidney capsule in large cell numbers, SSCs form bone and cartilage in a morphologically correct manner (124)(125)(126)(127), with a bone marrow cavity containing host-derived HSCs and blood vessels. Of the stromal cell subsets, at least one was in the Whitlock clones (121), and at least three of the stroma support HSCs and hematopoiesis (124-127).…”