Feasibility of intranasal human milk as stem cell therapy in preterm infants with intraventricular hemorrhage.

Objective: Intraventricular hemorrhage (IVH) is a common cause of preterm brain injury. Fresh parent's own milk (POM) contains pluripotent stem cells (SCs) that produce neuronal cells in-vitro. The permeable neonatal blood brain barrier potentially allows SC delivery.

Combination human umbilical cord perivascular and endothelial colony forming cell therapy for ischemic cardiac injury.

Cell-based therapeutics are promising interventions to repair ischemic cardiac tissue. However, no single cell type has yet been found to be both specialized and versatile enough to heal the heart. The synergistic effects of two regenerative cell types including endothelial colony forming cells (ECFC) and first-trimester human umbilical cord perivascular cells (FTM HUCPVC) with endothelial cell and pericyte properties respectively, on angiogenic and regenerative properties were tested in a rat model of myocardial infarction (MI), in vitro tube formation and Matrigel plug assay.

First trimester human umbilical cord perivascular cells (HUCPVC) modulate the kynurenine pathway and glutamate neurotransmission in an LPS-induced mouse model of neuroinflammation.

Background: The Kynurenine Pathway (KP) of tryptophan degradation and glutamate toxicity is implicated in several neurological disorders, including depression. The therapeutic potential of mesenchymal stromal cells (MSC), owing to their well documented phagocytosis-driven mechanism of immunomodulation and neuroprotection, has been tested in many neurological disorders. However, their potential to influence KP and the glutamatergic system has not yet been investigated.

Germ Cell-Specific Proteins AKAP4 and ASPX Facilitate Identification of Rare Spermatozoa in Non-Obstructive Azoospermia.

Non-obstructive azoospermia (NOA), the most severe form of male infertility, could be treated with intracytoplasmic sperm injection, providing spermatozoa were retrieved with the microdissection testicular sperm extraction (mTESE). We hypothesized that testis-specific and germ cell-specific proteins would facilitate flow cytometry-assisted identification of rare spermatozoa in semen cell pellets of NOA patients, thus enabling non-invasive diagnostics prior to mTESE. Data mining, targeted proteomics, and immunofluorescent microscopy identified and verified a panel of highly testis-specific proteins expressed at the continuum of germ cell differentiation.

Time course and mechanistic analysis of human umbilical cord perivascular cell mitigation of lipopolysaccharide-induced systemic and neurological inflammation.

Background Aims: Because of their potent immunomodulatory and anti-inflammatory properties, mesenchymal stromal cells are a major focus in the field of stem cell therapy. However, the precise mechanisms underlying this are not entirely understood. Human umbilical cord perivascular cells (HUCPVCs) are a promising cell therapy candidate.

Human umbilical cord perivascular cells prevent chemotherapeutic drug-induced male infertility in a mouse model.

Objective: To study whether intratesticular (IT) administration of 2 sources of human umbilical cord perivascular cells (HUCPVC), rich and potent sources of mesenchymal stromal cells (MSC), before chemotherapy can prevent infertility in a mouse model.

Design: Two control groups of CD1 male mice without busulfan (BUS) administration (untreated and IT media injection groups) were included. Experimental groups included IT administration of media, first trimester (FTM) HUCPVCs or term HUCPVCs (n = 5 each) injected 3 days before BUS treatment (20 mg/kg).

Human umbilical cord perivascular cells maintain regenerative traits following exposure to cyclophosphamide.

Chemotherapies can cause germ cell depletion and gonadal failure. When injected post-chemotherapy, mesenchymal stromal cells (MSCs) from various sources have been shown to have regenerative effects in rodent models of chemotherapy-induced gonadal injury. Here, we evaluated two properties of a novel source of MSC, first trimester (FTM) human umbilical cord perivascular cells (HUCPVCs) (with increased regenerative potential compared to older sources), that may render them a promising candidate for chemotherapeutic gonadal injury prevention.

Axon Degeneration Is Rescued with Human Umbilical Cord Perivascular Cells: A Potential Candidate for Neuroprotection After Traumatic Brain Injury.

Traumatic brain injury (TBI) leads to delayed secondary injury events consisting of cellular and molecular cascades that exacerbate the initial injury. Human umbilical cord perivascular cells (HUCPVCs) secrete neurotrophic and prosurvival factors. In this study, we examined the effects of HUCPVC in sympathetic axon and cortical axon survival models and sought to determine whether HUCPVC provide axonal survival cues.

Mesenchymal Stromal Cells Modulate Peripheral Stress-Induced Innate Immune Activation Indirectly Limiting the Emergence of Neuroinflammation-Driven Depressive and Anxiety-like Behaviors.

Background: Hyperactivation of innate immunity has been implicated in the etiology of mood disorders, including major depressive disorder (MDD). Mesenchymal stromal cells (MSCs) have demonstrated potent immunomodulatory capabilities in the context of chronic inflammatory disease and injury but have yet to be evaluated in stress-based preclinical models of MDD. We sought to test the ability of intravenous MSCs to modulate innate immune activation and behavioral patterns associated with repeated social defeat (RSD).

Pericytes in the Umbilical Cord.

The structural components of the umbilical cord, including two arteries and one vein, the stromal region/Wharton's jelly, and amniotic epithelial membrane, are well described at various time points of gestation. Over the last two decades, evidence has emerged that multipotent cells sharing properties of mesenchymal stromal cell and pericytes/mural cells can be isolated from multiple regions of the umbilical cord, including the perivascular region of the umbilical cord arteries and vein, Wharton's jelly, and subamnion. These cells have increasingly gained interest for their potential use in regenerative and immunomodulatory medicine.

Initial germ cell to somatic cell ratio impacts the efficiency of SSC expansion in vitro.

Unlabelled: Spermatogonial Stem Cell (SSC) expansion in vitro remains a major challenge in efforts to preserve fertility among pubertal cancer survivor boys. The current study focused on innovative approaches to optimize SSC expansion. Six- to eight-week-old CD-1 murine testicular samples were harvested by mechanical and enzymatic digestion.

Angiogenic potency evaluation of cell therapy candidates by a novel application of the in vitro aortic ring assay.

Background: Due to limitations of current angiogenesis assays, we aimed to develop a novel application of the rat aortic ring assay to assess the angiogenic potential of mesenchymal stromal cells (MSCs). First-trimester human umbilical cord-derived perivascular cells (FTM HUCPVCs) have multipotent characteristics and previously demonstrated angiogenic potential. We compared the effect of this young source of MSCs and adult bone marrow stromal cells (BMSCs) on ex vivo aortic endothelial network formation.

Optimal culture conditions are critical for efficient expansion of human testicular somatic and germ cells in vitro.

Objective: To optimize culture conditions for human testicular somatic cells (TSCs) and spermatogonial stem cells.

Design: Basic science study.

Setting: Urology clinic and stem cell research laboratory.

In vitro generation of Sertoli-like and haploid spermatid-like cells from human umbilical cord perivascular cells.

Background: First trimester (FTM) and term human umbilical cord-derived perivascular cells (HUCPVCs), which are rich sources of mesenchymal stem cells (MSCs), can give rise to Sertoli cell (SC)-like as well as haploid germ cell (GC)-like cells in vitro using culture conditions that recapitulate the testicular niche. Gamete-like cells have been produced ex vivo using pluripotent stem cells as well as MSCs. However, the production of functional gametes from human stem cells has yet to be achieved.

Human umbilical perivascular cells: a novel source of MSCs to support testicular niche regeneration.

The expansion of functional testicular biopsy-derived human spermatogonial stem cells (hSSC) ex-vivo may enable the restoration of fertility in pre-pubertal males having undergone gonadotoxic therapies or men with severe male factor infertility. Various somatic cells are known to regulate SSC homeostasis and spermatogenesis in the developing and adult testis. Prior attempts to recapitulate this niche demonstrated the requirement of feeder cells, such as endogenous testicular somatic cells, for germ cell expansion ex-vivo.

In Vitro Differentiation of First Trimester Human Umbilical Cord Perivascular Cells into Contracting Cardiomyocyte-Like Cells.

Myocardial infarction (MI) causes an extensive loss of heart muscle cells and leads to congestive heart disease (CAD), the leading cause of mortality and morbidity worldwide. Mesenchymal stromal cell- (MSC-) based cell therapy is a promising option to replace invasive interventions. However the optimal cell type providing significant cardiac regeneration after MI is yet to be found.

Ontogeny of human umbilical cord perivascular cells: molecular and fate potential changes during gestation.

Human umbilical cord-derived perivascular cells (PVCs) are a recently characterized source of mesenchymal stromal cells that has gained much interest in the field of cellular therapeutics. However, very little is known about the changes in fate potential and restrictions that these cells undergo during gestational development. This study is the first to examine the phenotypic, molecular, and functional properties of first trimester (FTM)-derived PVCs, outlining properties that are unique to this population when compared to term (TERM) counterparts.

CBP histone acetyltransferase activity regulates embryonic neural differentiation in the normal and Rubinstein-Taybi syndrome brain.

Increasing evidence indicates that epigenetic changes regulate cell genesis. Here, we ask about neural precursors, focusing on CREB binding protein (CBP), a histone acetyltransferase that, when haploinsufficient, causes Rubinstein-Taybi syndrome (RTS), a genetic disorder with cognitive dysfunction. We show that neonatal cbp(+/-) mice are behaviorally impaired, displaying perturbed vocalization behavior.

Home at last: neural stem cell niches defined.

Adult neural stem cells (NSCs) are involved in regulating mammalian behavior and are controlled by diverse external stimuli. Improved understanding of the physical location of NSCs and the microenvironmental cues that regulate their behavior, which combine to define the NSC "home," or niche, may reveal how to control their function.

Lfc and Tctex-1 regulate the genesis of neurons from cortical precursor cells.

The mechanisms that regulate symmetric, proliferative divisions versus asymmetric, neurogenic divisions of mammalian neural precursors are still not well understood. We found that Lfc (Arhgef2), a Rho-specific guanine nucleotide exchange factor that interacts with spindle microtubules, and its negative regulator Tctex-1 (Dynlt1) determine the genesis of neurons from precursors in the embryonic murine cortex. Specifically, genetic knockdown of Arhgef2 in cortical precursors either in culture or in vivo inhibited neurogenesis and maintained cells as cycling radial precursors.