CD271 antigen defines a subset of multipotent stromal cells with immunosuppressive and lymphohematopoietic engraftment-promoting properties

Abstract

BackgroundIn vitro proliferative and differentiation potential of mesenchymal stromal cells generated from CD271 + bone marrow mononuclear cells (CD271-mesenchymal stromal cells) has been demonstrated in several earlier and recent reports. In the present study we focused, in addition to proliferative and differentiation potential, on in vitro and in vivo immunosuppressive and lymphohematopoietic engraftment-promoting potential of these mesenchymal stromal cells compared to bone marrow-derived mesenchymal stromal cells generated by plastic adherence (plastic adherence-mesenchymal stromal cells). Design and MethodsWe set up a series of experimental protocols in order to determine the phenotype of CD271-mesenchymal stromal cells, and their clonogenic, proliferative, differentiation and immunosuppressive potential. The potential of CD271-mesenchymal stromal cells to improve the engraftment of CD133 + hematopoietic stem cells at co-transplantation was evaluated in immunodeficient NOD/SCID-IL2Rg null mice. ResultsIn vitro studies demonstrated that CD271-mesenchymal stromal cells differentiate along adipogenic, osteogenic and chondrogenic lineages (trilineage potential), produce significantly higher levels of cytokines than plastic adherence-mesenchymal stromal cells, and significantly inhibit the proliferation of allogeneic T-lymphocytes in mixed lymphocyte reaction assays. Elevated levels of prostaglandin E2, but not nitric monoxide, mediated the majority of this immunosuppressive effect. In vivo studies showed that CD271-mesenchymal stromal cells promoted significantly greater lymphoid engraftment than did plastic adherence-mesenchymal stromal cells when co-transplanted with CD133 + hematopoietic stem cells at a ratio of 8:1 in immunodeficient NOD/SCID-IL2Rg null mice. They induced a 10.4-fold increase in the number of T cells, a 2.5-fold increase in the number of NK cells, and a 3.6-fold increase in the number of B cells, indicating a major qualitative difference between these two mesenchymal stromal cell populations. ConclusionsOur results indicate that CD271 antigen provides a versatile marker for prospective isolation and expansion of multipotent mesenchymal stromal cells with immunosuppressive and lymphohematopoietic engraftment-promoting properties. The co-transplantation of such cells together with hematopoietic stem cells in patients with hematologic malignancies may prove valuable in the prevention of impaired/delayed T-cell recovery and graft-versus-host disease.Key words: T-cell recovery, graft-versus-host disease, MSC.Citation: Kuçi S, Kuçi Z, Kreyenberg H, Deak E, Pütsch K, Huenecke S, Amara C, Koller S, Rettinger E, Grez M, Koehl U, Henschler R, Tonn T, von Laer D, Klingebiel T, and Bader P. CD271 antigen defines a subset of multipotent stromal cells with immunosuppressive and lymphohematopoietic engraftment-promoting properties. Haematologica. 2010;95:651-659. doi:10.3324/haematol.2009 This is an open-access paper. © F e r r a t a S t o r t i F o u n d a t i o n CD271 antigen defines a subset of m...

Mesenchymal stromal cells: a novel and effective strategy for facilitating engraftment and accelerating hematopoietic recovery after transplantation?

“…38 In non-human primates, co-transplantation of MSCs improved HC engraftment after autologous intra-BM transplantation and this was associated with increased chimerism in the peripheral blood. 39 As already mentioned above, Kuci et al 13 showed that CD271 þ MSCs were capable of promoting significantly greater lymphoid engraftment, as compared to an unselected population of plastic-adherent MSCs, when co-transplanted with CD133 þ HCs in NOD/SCID mice.…”

“…13 Plateletderived growth factor receptor-b (CD140b) has been also identified as a selective marker for the isolation of clonogenic MSCs; 11 an STRO-4 MoAb has been shown to be specific for mesenchymal precursors cells from human and ovine tissues, being capable of enriching colonyforming fibroblasts when employed for MSC isolation from BM. 14 Despite the identification of these new MSC markers, [8][9][10][11][12][13][14] none of the available reagents has been shown to be singularly capable of identifying the true mesenchymal progenitors. Future research should include the identification of MSC-specific markers, which will hopefully allow one to dissect the developmental hierarchy of MSCs and will facilitate the generation of homogeneous cellular products.…”

“…6,7 Recently, the identification and prospective isolation of mesenchymal progenitors, both in murine and human adult BM, have been reported, based on the expression of specific markers. [8][9][10][11][12][13][14] Whether culture-expanded MSCs differ from their progenitors in vivo is uncertain, as proliferation on plastic surfaces and culture conditions may induce both phenotypic and functional changes. Anjos-Afonso et al 8 have reported the identification, isolation and characterization of a population of multipotent mesenchymal cells in murine BM, based on the expression of the stage-specific embryonic antigen-1.…”

LNGFR (CD271) as Marker to Identify Mesenchymal Stem Cells from Different Human Sources: Umbilical Cord Blood, Wharton?s Jelly and Bone Marrow

“…Although CD271 was initially believed to be expressed by cells of the nervous system and plays a key role in the development, survival and differentiation of neural cells, it is now known to be a member of the low-affinity neurotrophin receptor and tumor necrosis factor receptor superfamily [18]. Thus, CD271 has been proposed as a versatile marker to selectively isolate and expand multipotent MSCs with both immunosuppressive and lymphohematopoietic engraftmentpromoting properties [19][20][21].…”

Influência da desnutrição proteica sobre a expressão de fatores de transcrição envolvidos no processo de diferenciação da célula tronco mesenquimal medular

“…Sendo atualmente aceito para caracterizá-la: a) capacidade de aderência ao plástico nas condições usuais de cultivo; b) expressão antigênica para os antígenos CD105, CD73, CD90, CD13, CD49e, CD271 e ≤ 2% (ausência de expressão) para os antígenos CD45, CD34 e CD14; c) diferenciação in vitro em osteoblastos, adipócitos e condrócitos (DOMINICI et al, 2006;KUÇI et al, 2010;WU, 2011).…”