Isolation and characterization of Oct-4+/HLA-G+ mesenchymal stem cells from human umbilical cord matrix: differentiation potential and detection of new markers

Abstract

The presence of multipotent cells in several adult and embryo-related tissues opened new paths for their use in regenerative medicine. Extraembryonic tissues such as umbilical cord are considered a promising source of stem cells, potentially useful in therapy. The characterization of cells from the umbilical cord matrix (Wharton's Jelly) and amniotic membrane revealed the presence of a population of mesenchymal-like cells, sharing a set of core-markers expressed by "mesenchymal stem cells". Several reports enlightened the differentiation capabilities of these cells, even if at times the lack of an extensive characterization of surface markers and immune co-stimulators expression revealed hidden pitfalls when in vivo transplantation was performed. The present work describes a novel isolation protocol for obtaining mesenchymal stem cells from the umbilical cord matrix. These cells are clonogenic, retain long telomeres, can undergo several population doublings in vitro, and can be differentiated in mature mesenchymal tissues as bone and adipose. We describe for the first time that these cells, besides expressing all of the core-markers for mesenchymal stem cells, feature also the expression, at both protein and mRNA level, of tolerogenic molecules and markers of all the three main lineages, potentially important for both their differentiative potential as well as immunological features.

Novel Immunomodulatory Markers Expressed by Human WJ-MSC: an Updated Review in Regenerative and Reparative Medicine

“…As depicted in Table 1, and as reported by us and others, HLA-G is expressed by WJ-MSC [16,47] and BM-MSC [48]. HLA-G has a key role in tolerance induction of the mother's immune system towards the semi-allogeneic foetus during pregnancy; it acts together with other class Ib MHC molecules (such as HLA-E and HLA-F) and trophoblast-secreted factors as EPF (early pregnancy factor) [77,78].…”

“…WJ-MSC do express the core markers CD29, CD44, CD73, CD90, CD105, together with class Ia MHC (major histocompatibility complex) molecules (as HLA-A, -B, -C). WJ-MSC do not express hematopoietic and endothelial markers (CD34, CD45, CD31, vWF) and class II MHC (HLA-DR) as well [13][14][15][16]. In addition, WJ-MSC may express CD117 (receptor for the stem cell factor, encoded by c-Kit gene) and, differently to BM-MSC, CD68 and CD14 [12,16,17].…”

“…For example, cytoskeletal molecules of various classes such as: α-smooth muscle actin and vimentin (mainly expressed in mesenchymal lineage cells); nestin and GFAP (glial fibrillar acidic protein) (featured by mature cells of neuroectodermal lineage); cytokeratin-8, -18 and -19 (expressed in endoderm-derived epithelial cells) [16,19]. The presence of such molecules may partly reflect the capacity of these cells to differentiate towards mature cell types derived from all three germ layers, thank to their intrinsic ability to cross germ layers boundaries: indeed, WJ-MSC are defined as multipotent stem cells since they can differentiate into at least three different cellular lineages: osteoblasts, adipocytes and chondrocytes [19,20], even though their differentiative ability is largely wider [21,22].…”

“…In addition, the expression of connexin 43 [16] suggested the possibility to differentiate WJ-MSC into cardiomyocytes or other cardiac resident cell types [31] or to be directly administered to correct conduction defects and other heart diseases [32][33][34].…”

Neural differentiation of human umbilical cord matrix-derived mesenchymal cells under special culture conditions

“…MSCs isolated from Wharton's Jelly (hUCMs (were shown to have surface markers, immune properties (Fong et al 2011;Weiss et al 2006), and differentiation potential towards cells with mesoderm offspring (Penolazzi et al 2009;Schneider et al 2010), including adipose, bone, cartilage, skeletal muscle, endothelium, cardiomyocyte and neuronal cells (Ishige et al 2009;Leeb et al 2009;Penolazzi et al 2009;Wu et al 2007), allowing replacement of ectodermal and mesodermal tissues (Schneider et al 2010). Several reports have characterized the in vitro differentiation capabilities of hUCM cells (La Rocca et al 2009) into neuron like cells (Abdulrazzak et al 2010;Cao and Feng 2009;Hu et al 2009;Zhang et al 2009b). Early studies focused on the differentiation of MSCs into neurons and detection of astrocyte markers received only modest attention (Boucherie and Hermans 2009).…”