Increased Haematopoietic Supportive Function of USSC from Umbilical Cord Blood Compared to CB MSC and Possible Role of DLK-1

Abstract

Multipotent stromal cells can be isolated from a variety of different tissues in the body. In contrast to stromal cells from the adult bone marrow (BM) or adipose tissue, cord blood (CB) multipotent stromal cells (MSC) are biologically younger. Since first being described by our group, delta like 1 homologue (DLK-1) was determined as a discriminating factor between the distinct cord blood-derived subpopulations: the unrestricted somatic stromal cells (USSC), which lack adipogenic differentiation capacity, and the BM MSC-like CB MSC. In this study, experiments assessing the haematopoiesis-supporting capacity and molecular biological analyses were conducted and clearly confirmed different properties. Compared to CB MSC, USSC lead to a higher expansion of haematopoietic cells and in addition express significantly higher levels of insulin-like growth factor binding protein 1 (IGFBP1), but lower levels of IGF2. The data presented here also indicate that DLK-1 might not be the sole factor responsible for the inhibition of adipogenic differentiation potential in USSC but nevertheless indicates a biological diversity among cord blood-derived stromal cells.

DNA Damage Response in Neonatal and Adult Stromal Cells Compared With Induced Pluripotent Stem Cells

“…Neonatal USSCs can be easily differentiated into the osteogenic and chondrogenic lineage in vitro but can only be differentiated into the adipogenic lineage after coculture with CB MSCs [33]. Detailed characterization of the individual inherent differentiation capacity is available [30, 34–36]. Therefore, neonatal stromal cells (like USSCs) can be assumed to provide favorable features for developmental toxicity testing to assess the potential toxicity of drug candidates and chemicals in the neonatal system [37].…”

Early Postnatal Expression of Tgfβ-1 and Fgf-2 Correlates With Regenerative Functions of Unrestricted Somatic Stem Cell Infusion After Rabbit GMH-IVH

“… 29-33 Kogler et al and our group characterized human cord blood (hCB)-derived unrestricted somatic stem cells (USSCs) and studied their proliferation, expansion, gene and cytokine expression, epigenetic modification, and lineage differentiation in various models. 34-37 We were the first to demonstrate that USSCs migrate to the site of injury, suppress inflammation, reduce hydrocephalus, improve myelination as well as neurodevelopmental outcomes in a premature rabbit pup model of IVH. 38 , 39 Other investigators show that USSCs induce significant axonal regrowth and effectively improve long-term functional locomotory and neurobehavioral recovery.…”

Comparing the Gene Expression Profile of Stromal Cells from Human Cord Blood and Bone Marrow: Lack of the Typical “Bone” Signature in Cord Blood Cells

“…Former results indicated a correlation of the absent adipogenic potential and the expression of DLK1 (delta, Drosophila homolog-like 1) in USSC, since USSC but not CBSC express DLK1 [5]. Recent results suggested that DLK1 might not be the sole factor responsible for the inhibition of in vitro adipogenesis in USSC [6]. In microarray and PCR analyses, the expression of HOX (homeobox) genes was defined as additional distinguishing feature: USSC completely lack HOX gene expression, while CBSC are HOX positive [7].…”

“…In microarray and PCR analyses, the expression of HOX (homeobox) genes was defined as additional distinguishing feature: USSC completely lack HOX gene expression, while CBSC are HOX positive [7]. Furthermore, USSC can be discriminated from CBSC on the basis of their higher hematopoiesis-supporting capacity in coculture experiments [6]. …”