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

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

Hematopoietic stem cells in neonates: any differences between very preterm and term neonates?

In the last decades, human full-term cord blood was extensively investigated as a potential source of hematopoietic stem and progenitor cells (HSPCs). Despite the growing interest of regenerative therapies in preterm neonates, only little is known about the biological function of HSPCs from early preterm neonates under different perinatal conditions. Therefore, we investigated the concentration, the clonogenic capacity and the influence of obstetric/perinatal complications and maternal history on HSPC subsets in preterm and term cord blood.CD34+ HSPC subsets in UCB of 30 preterm and 30 term infants were evaluated by flow cytometry. Clonogenic assays suitable for detection of the proliferative potential of HSPCs were conducted. Furthermore, we analyzed the clonogenic potential of isolated HSPCs according to the stem cell marker CD133 and aldehyde dehydrogenase (ALDH) activity.Preterm cord blood contained a significantly higher concentration of circulating CD34+ HSPCs, especially primitive progenitors, than term cord blood. The clonogenic capacity of HSPCs was enhanced in preterm cord blood. Using univariate analysis, the number and clonogenic potential of circulating UCB HSPCs was influenced by gestational age, birth weight and maternal age. Multivariate analysis showed that main factors that significantly influenced the HSPC count were maternal age, gestational age and white blood cell count. Further, only gestational age significantly influenced the clonogenic potential of UCB HSPCs. Finally, isolated CD34+/CD133+, CD34+/CD133- and ALDH(high) HSPC obtained from preterm cord blood showed a significantly higher clonogenic potential compared to term cord blood.We demonstrate that preterm cord blood exhibits a higher HSPC concentration and increased clonogenic capacity compared to term neonates. These data may imply an emerging use of HSPCs in autologous stem cell therapy in preterm neonates

Obstretic, perinatal and neonatal clinical parameters.

<p>Data are shown as mean ± SD (median) or n (%), SGA: small-for-gestational-age; PROM: prolonged rupture of membranes.</p><p>Obstretic, perinatal and neonatal clinical parameters.</p

Clonogenic capacity of HSPCs of preterm and term cord blood.

<p>Clonogenic potential of HSCs in the lysed whole blood assay (LWBA, n = 15) and sorted HSC subpopulations (n = 3).</p><p>Clonogenic capacity of HSPCs of preterm and term cord blood.</p

HSPC subsets and WBC count of preterm and term cord blood.

<p>PCB: preterm cord blood; TCB: term cord blood; WBC: white blood cells; HSPC: hematopoietic stem and progenitor cells.</p><p>HSPC subsets and WBC count of preterm and term cord blood.</p

HSPC count and correlation with clinical parameters.

<p>Number of circulating HSPCs in umbilical cord blood of preterm and term neonates (A) and in ELBW, VLBW, LBW and appropriate for gestational age (AGA) infants (B). Correlation between number of HSPCs and maternal age of PCB (C) and TCB (D), gestational age (E) and birth weight (F).</p