Potential Application of Cord Blood-Derived Stromal Cells in Cellular Therapy and Regenerative Medicine

Abstract

Neonatal stromal cells from umbilical cord blood (CB) are promising alternatives to bone marrow- (BM-) derived multipotent stromal cells (MSCs). In comparison to BM-MSC, the less mature CB-derived stromal cells have been described as a cell population with higher differentiation and proliferation potential that might be of potential interest for clinical application in regenerative medicine. Recently, it has become clear that cord blood contains different stromal cell populations, and as of today, a clear distinction between unrestricted somatic stromal cells (USSCs) and CB-MSC has been established. This classification is based on the expression of DLK-1, HOX, and CD146, as well as functional examination of the adipogenic differentiation potential and the capacity to support haematopoiesis in vitro and in vivo. However, a marker enabling a prospective isolation of the rare cell populations directly out of cord blood is yet to be found. Further analysis may help to reveal even more subpopulations with different properties, which could be useful for the directed application of these cells in preclinical models.

Low oxygen tension reveals distinctHOXcodes in human cord blood-derived stromal cells associated with specific endochondral ossification capacitiesin vitroandin vivo

“…Besides the complex regulation of chondro‐osteogenic marker genes in the HOX expression background of a cell, strong inherent cell heterogeneity, on a bulk and not clonal level, may lead to misinterpretation of data (Kluth et al , ; McKenna et al , ; Viswanathan et al , ). Here, clonally derived cell lines were applied and subtypes defined by specific HOX codes.…”

Stem Cells

“…The currently used term, mesenchymal stem cell (MSC) , was first proposed in 1991 based on the capacity to differentiate into cells of the mesenchymal lineage (bone, cartridge, tendon, ligament, BM stroma, adipocytes, dermis, muscle, and connective tissue) 57 . However, the “multipotency” of MSCs remains controversial 56;58 . Furthermore, while MSCs are often referred to as “stem cells”, they do not meet strict criteria regarding self-renewal capacity and multilineage potential at the single cell level 55 .…”

Osteoconduction of Unrestricted Somatic Stem Cells on an Electrospun Polylactic-Co-Glycolic Acid Scaffold Coated with Nanohydroxyapatite

“…Indeed, the ability to manage the differentiation of MSCs makes them a suitable cell source for bone tissue engineering [Yousefi et al, 2016]. Among different MSC types, MSCs derived from cord blood have been recognized as a valuable cell source which can be noninvasively and ethically collected [Kluth et al, 2012;Bosch et al, 2013;Kluth et al, 2013].…”

“…The presence of nonhematopoietic and multipotent stem cells in cord blood was primarily defined by Erices et al [2000], and later Kogler et al [2004] published a technique for the isolation of stem cells from cord blood [Kluth et al, 2012]. In vitro, these stem cells have the potential to differentiate into osteoblasts, adipocytes, chondrocytes, keratinocytes, and hematopoietic and neuronal cells while in vivo differentiation leads to the appearance of bone, cartilage, hepatocytes, hematopoietic cells, and myocytes, for example [Kögler et al, 2004;Liao et al, 2014].…”

“…In vitro, these stem cells have the potential to differentiate into osteoblasts, adipocytes, chondrocytes, keratinocytes, and hematopoietic and neuronal cells while in vivo differentiation leads to the appearance of bone, cartilage, hepatocytes, hematopoietic cells, and myocytes, for example [Kögler et al, 2004;Liao et al, 2014]. In comparison with bone marrow-derived stromal cells (BMSCs), cord blood-derived stem cells, originally termed unrestricted somatic stem cells (USSCs), have several benefits such as noninvasive collection, abundant availability, higher immaturity, higher differentiation, and faster proliferation [Wang et al, 2011;Kluth et al, 2012;Bosch et al, 2013]. Although primary frequency of USSCs is really low in cord blood, they can be divided into at least 10 15 cells while keeping their normal karyotype [Kögler et al, 2004].…”