isolation-characterization-human-umbilical-cord-derived-mesenchymal

Isolation and Characterization of Human Umbilical Cord-derived Mesenchymal Stem Cells from Preterm and Term Infants

Mesenchymal stem cells (MSCs) have considerable therapeutic potential and attract increasing interest in the biomedical field. MSCs are originally ...

Harlequin ichthyosis (HI) is the most severe form of autosomal recessive congenital ichthyosis, with a high mortality rate. Recent advances in neonatal care and the early administration of retinoids have improved the survival rate of HI. Here, we present a case of HI who was successfully treated with early administration of etretinate and showed good prognosis. Next-generation sequencing identified novel mutations of the ATP-binding cassette subfamily A member 12 gene (ABCA12), c.5884+4_+5delAA and c.7239G>A, which caused skipping of exons 39 and 48, respectively. Transcripts with exon 48 skipping, which cause a deletion in the second ATP-binding cassette of ABCA12, were dominantly expressed in the skin. Besides the early administration of etretinate, the differential expression of the mutant protein with limited segmental deletion of ABCA12 may be related to the favorable outcome of our patient.

Case of harlequin ichthyosis with a favorable outcome: Early treatment and novel, differentially expressed, alternatively spliced transcripts of the ATP-binding cassette subfamily A member 12 gene.

Spinal muscular atrophy (SMA) is the most common genetic neurological disease leading to infant death. It is caused by loss of survival motor neuron (SMN) 1 gene and subsequent reduction of SMN protein in motor neurons. Because SMN is ubiquitously expressed and functionally linked to general RNA metabolism pathway, fibroblasts (FBs) are most widely used for the assessment of SMN expression in SMA patients but usually isolated from skin biopsy samples after the onset of overt symptoms. Although recent translational studies of SMN-targeted therapies have revealed the very limited time window for effective SMA therapies during perinatal period, the exact time point when SMN shortage became evident is unknown in human samples. In this study, we analyzed SMN mRNA and protein expression during perinatal period by using umbilical cord-derived mesenchymal stem cells (UC-MSCs) obtained from preterm and term infants.

Gestational Age-Dependent Increase of Survival Motor Neuron Protein in Umbilical Cord-Derived Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are a heterogeneous cell population that is isolated initially from the bone marrow (BM) and subsequently almost all tissues including umbilical cord (UC). UC-derived MSCs (UC-MSCs) have attracted an increasing attention as a source for cell therapy against various degenerative diseases due to their vigorous proliferation and differentiation. Although the cell proliferation and differentiation of BM-derived MSCs is known to decline with age, the functional difference between preterm and term UC-MSCs is poorly characterized. In the present study, we isolated UC-MSCs from 23 infants delivered at 22-40 weeks of gestation and analyzed their gene expression and cell proliferation. Microarray analysis revealed that global gene expression in preterm UC-MSCs was distinct from term UC-MSCs. WNT signaling impacts on a variety of tissue stem cell proliferation and differentiation, and its pathway genes were enriched in differentially expressed genes between preterm and term UC-MSCs. Cell proliferation of preterm UC-MSCs was significantly enhanced compared to term UC-MSCs and counteracted by WNT signaling inhibitor XAV939. Furthermore, WNT2B expression in UC-MSCs showed a significant negative correlation with gestational age (GA). These results suggest that WNT signaling is involved in the regulation of GA-dependent UC-MSC proliferation.

Article	Year
Case of harlequin ichthyosis with a favorable outcome: Early treatment and novel, differentially expressed, alternatively spliced transcripts of the ATP-binding cassette subfamily A member 1... The Journal of dermatology\| PubMed ID: 28295493	2017
Gestational Age-Dependent Increase of Survival Motor Neuron Protein in Umbilical Cord-Derived Mesenchymal Stem Cells. Frontiers in pediatrics\| PubMed ID: 28929094	2017
Involvement of WNT Signaling in the Regulation of Gestational Age-Dependent Umbilical Cord-Derived Mesenchymal Stem Cell Proliferation. Stem cells international\| PubMed ID: 29138639	2017

Tsubasa Koda

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