Low-affinity Nerve Growth Factor Receptor (CD271) Heterogeneous Expression in Adult and Fetal Mesenchymal Stromal Cells

Abstract

Human multipotent mesenchymal stromal cells (MSC) are isolated from a plethora of tissue sources for cell therapy purposes. In 2006, the International Society for Cellular Therapy (ISCT) published minimal guidelines to define MSC identity. Nevertheless, many independent studies demonstrated that cells meeting the ISCT criteria possessed heterogeneous phenotypes and functionalities, heavily influenced by culture conditions. In this study, human MSC derived from many adult (bone marrow and adipose tissue) or fetal (cord blood, Wharton’s jelly, umbilical cord perivascular compartment and amniotic fluid) tissues were investigated. Their immunophenotype was analyzed to define consistent source-specific markers by extensive flow cytometry analysis and real-time qRT-PCR. CD271+ subpopulations were detected in adult MSC, whereas NG2 was significantly more expressed in fetal MSC but failed validation on independent samples coming from an external laboratory. The highest number of CD271+ adult MSC were detected soon after isolation in serum-based culture conditions. Furthermore, heterogeneous percentages of CD271 expression were found in platelet lysate-based or serum-free culture conditions. Finally, CD271+ adult MSC showed high clonogenic and osteogenic properties as compared to CD271− cells. To conclude, in this phenotype-function correlation study CD271+ subpopulation confers heterogeneity on adult MSC, confirming the need of more specific markers to address MSC properties.

Age-related inflammation triggers skeletal stem/progenitor cell dysfunction

“…To investigate a clinically relevant age-associated effect on skeletal stem cell frequency and function, we first examined iliac crest bone graft (ICBG) samples from 36 patients (20 male, 16 female) with ages ranging from 24 to 89 y who underwent operative fixation of an upper-or lower-extremity fracture. FACS with CD271 as a human skeletal stem cell marker (8)(9)(10)(11) revealed that SSPC frequency significantly declined with increasing age ( Fig. 1 A and B).…”

“…FACS analysis was performed by using a BD LSRII cell analyzer with high-throughput sampler. CD45-negative and CD271-positive SSPCs were displayed as percentages of total single cell number (8)(9)(10)(11). Patient data, including radiographic and clinical time to union, were extracted from a prospective patient database at the NYU Langone Orthopedic Hospital.…”

Maternal Serum, an Isolation and Expansion Tool for Umbilical Cord Matrix Mesenchymal Stromal Cells

“…There is a belief that the minimal criteria set out by the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy are no longer a robust enough method of determining MSC authenticity [30], as they could be used to characterise fibroblastic cell strains [31]. Moreover, there are reports in the literature supporting a theory that transplanted MSCs themselves do not differentiate to form new tissue in vivo, but rather migrate to a site of injury or disease and secrete factors which stimulate the resident stem cells to construct new tissue [32].…”

Rat Olfactory Mucosa Mesenchymal Stem/Stromal Cells (OM-MSCs): A Characterization Study

“…Concerning the capacity for differentiation, multiple studies carried out have made it possible to perceive that MSCs are capable not only of traditional tridifferentiation but also of originating other cells and tissues with mesodermal (ligaments, tendons, cardiomyocytes, muscles), ectodermal and endodermal origin (skin, retina, lungs, hepatocytes, renal tubes, pancreatic islets, sebaceous glands and ducts and neural cells) [12]. Also, recently new markers have been explored to identify those that can be considered stemness-associated MSC stromal cell markers, in opposition to the traditional MSC markers that some authors question and indicate as more appropriate to be considered stromal cell markers [13]. In this group, CD271 is indicated as a potential precursor for homogeneous subpopulations of MSCs and described as a way to improve culture homogeneity.…”