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1.  Umbilical cord blood mesenchymal stem cells protect amyloid-β42 neurotoxicity via paracrine 
World Journal of Stem Cells  2012;4(11):110-116.
AIM: To understand the neuroprotective mechanism of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) against amyloid-β42 (Aβ42) exposed rat primary neurons.
METHODS: To evaluate the neuroprotective effect of hUCB-MSCs, the cells were co-cultured with Aβ42-exposed rat primary neuronal cells in a Transwell apparatus. To assess the involvement of soluble factors released from hUCB-MSCs in neuroprotection, an antibody-based array using co-cultured media was conducted. The neuroprotective roles of the identified hUCB-MSC proteins was assessed by treating recombinant proteins or specific small interfering RNAs (siRNAs) for each candidate protein in a co-culture system.
RESULTS: The hUCB-MSCs secreted elevated levels of decorin and progranulin when co-cultured with rat primary neuronal cells exposed to Aβ42. Treatment with recombinant decorin and progranulin protected from Aβ42-neurotoxicity in vitro. In addition, siRNA-mediated knock-down of decorin and progranulin production in hUCB-MSCs reduced the anti-apoptotic effects of hUCB-MSC in the co-culture system.
CONCLUSION: Decorin and progranulin may be involved in anti-apoptotic activity of hUCB-MSCs exposed to Aβ42.
PMCID: PMC3536832  PMID: 23293711
Human umbilical cord blood-derived mesenchymal stem cells; Decorin; Progranulin; Aβ42; Anti-apoptosis
2.  Application of human umbilical cord blood-derived mesenchymal stem cells in disease models 
World Journal of Stem Cells  2010;2(2):34-38.
Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) are regarded as an alternative source of bone marrow-derived mesenchymal stem cells because collection of cord blood is less invasive than that of bone marrow. hUCB-MSCs have recently been studied for evaluation of their potential as a source of cell therapy. In this review, the general characteristics of hUCB-MSCs and their therapeutic effects on various diseases in vitro and in vivo will be discussed.
PMCID: PMC3097922  PMID: 21607114
Regeneration; Immune modulation; Nursing effect; Mesenchymal stem cells
3.  Microarray analysis after umbilical cord blood derived mesenchymal stem cells injection in monocrotaline-induced pulmonary artery hypertension rats 
Anatomy & Cell Biology  2014;47(4):217-226.
Pulmonary arterial hypertension (PAH) is associated with structural alterations of lung vasculature. PAH is still a devastating disease needing an aggressive therapeutic approach. Despite the therapeutic potential of human umbilical cord mesenchymal stem cells (MSCs), the molecular parameters to define the stemness remain largely unknown. Using high-density oligonucleotide microarrays, the differential gene expression profiles between a fraction of mononuclear cells of human umbilical cord blood (UCB) and its MSC subpopulation were obtained. Of particular interest was a subset of 46 genes preferentially expressed at 7-fold or higher in the group treated with human UCB-MSCs. This subset contained numerous genes involved in the inflammatory response, immune response, lipid metabolism, cell adhesion, cell migration, cell differentiation, apoptosis, cell growth, transport, cell proliferation, transcription, and signal transduction. Our results provide a foundation for a more reproducible and reliable quality control using genotypic analysis for the definition of human UCB-MSCs. Therefore, our results will provide a basis for studies on molecular mechanisms controlling the core properties of human MSCs.
PMCID: PMC4276895  PMID: 25548719
Pulmonary hypertension; Monocrotaline; Umbilical mesenchymal stem cells; Microarray
4.  Comparative Analysis of Human Mesenchymal Stem Cells from Bone Marrow, Adipose Tissue, and Umbilical Cord Blood as Sources of Cell Therapy 
Various source-derived mesenchymal stem cells (MSCs) have been considered for cell therapeutics in incurable diseases. To characterize MSCs from different sources, we compared human bone marrow (BM), adipose tissue (AT), and umbilical cord blood-derived MSCs (UCB-MSCs) for surface antigen expression, differentiation ability, proliferation capacity, clonality, tolerance for aging, and paracrine activity. Although MSCs from different tissues have similar levels of surface antigen expression, immunosuppressive activity, and differentiation ability, UCB-MSCs had the highest rate of cell proliferation and clonality, and significantly lower expression of p53, p21, and p16, well known markers of senescence. Since paracrine action is the main action of MSCs, we examined the anti-inflammatory activity of each MSC under lipopolysaccharide (LPS)-induced inflammation. Co-culture of UCB-MSCs with LPS-treated rat alveolar macrophage, reduced expression of inflammatory cytokines including interleukin-1α (IL-1α), IL-6, and IL-8 via angiopoietin-1 (Ang-1). Using recombinant Ang-1 as potential soluble paracrine factor or its small interference RNA (siRNA), we found that Ang-1 secretion was responsible for this beneficial effect in part by preventing inflammation. Our results demonstrate that primitive UCB-MSCs have biological advantages in comparison to adult sources, making UCB-MSCs a useful model for clinical applications of cell therapy.
PMCID: PMC3794764  PMID: 24005862
umbilical cord blood; bone marrow; adipo tissue; mesenchymal stem cell; expansion; senescence; anti-inflammation; angiopoietin-1; cell therapy
5.  Safety and feasibility of countering neurological impairment by intravenous administration of autologous cord blood in cerebral palsy 
We conducted a pilot study of the infusion of intravenous autologous cord blood (CB) in children with cerebral palsy (CP) to assess the safety and feasibility of the procedure as well as its potential efficacy in countering neurological impairment.
Patients diagnosed with CP were enrolled in this study if their parents had elected to bank their CB at birth. Cryopreserved CB units were thawed and infused intravenously over 10~20 minutes. We assessed potential efficacy over 6 months by brain magnetic resonance imaging (MRI)-diffusion tensor imaging (DTI), brain perfusion single-photon emission computed tomography (SPECT), and various evaluation tools for motor and cognitive functions.
Twenty patients received autologous CB infusion and were evaluated. The types of CP were as follows: 11 quadriplegics, 6 hemiplegics, and 3 diplegics. Infusion was generally well-tolerated, although 5 patients experienced temporary nausea, hemoglobinuria, or urticaria during intravenous infusion. Diverse neurological domains improved in 5 patients (25%) as assessed with developmental evaluation tools as well as by fractional anisotropy values in brain MRI-DTI. The neurologic improvement occurred significantly in patients with diplegia or hemiplegia rather than quadriplegia.
Autologous CB infusion is safe and feasible, and has yielded potential benefits in children with CP.
PMCID: PMC3369209  PMID: 22443810
Cerebral palsy; Cord blood; Mononuclear cells; Cell therapy
6.  Cotransplanted Bone Marrow Derived Mesenchymal Stem Cells (MSC) Enhanced Engraftment of Hematopoietic Stem Cells in a MSC-dose Dependent Manner in NOD/SCID Mice 
Journal of Korean Medical Science  2006;21(6):1000-1004.
Transplantation of marrow-derived mesenchymal stem cells (MSCs), expanded by culture in addition to whole bone marrow, has been shown to enhance engraftment of human hematopoietic stem cells (HSCs). Our hypothesis was that there might be an optimum ratio range that could enhance engraftment. We examined the percent donor chimerism according to the ratio of HSCs to MSCs in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. We tested a series of ratios of co-transplanted CD34+-selected bone marrow cells, and marrow-derived MSCs into sublethally irradiated NOD/SCID mice. In all experiments, 1×105 bone marrow derived human CD34+ cells were administered to each mouse and human MSCs from different donors were infused concomitantly. We repeated the procedure three times and evaluated engraftment with flow cytometry four weeks after each transplantation. Serial ratios of HSCs to MSCs were 1:0, 1:1, 1:2 and 1:4, in the first experiment, 1:0, 1:1, 1:2, 1:4 and 1:8 in the second and 1:0, 1:1, 1:4, 1:8 and 1:16 in the third. Cotransplantation of HSCs and MSCs enhanced engraftment as the dose of MSCs increased. Our results suggest that the optimal ratio of HSCs and MSCs for cotransplantation might be in the range of 1:8-1:16; whereas, an excessive dose of MSCs might decrease engraftment efficiency.
PMCID: PMC2721918  PMID: 17179676
Hematopoietic Stem Cells; Mesenchymal Stem Cells; Transplantation; Mice, SCID; Engraftment
7.  Autologous bone marrow cell transplantation combined with off-pump coronary artery bypass grafting in patients with ischemic cardiomyopathy 
Canadian Journal of Surgery  2008;51(4):269-275.
Clinical studies have demonstrated that intracoronary or intramyocardial transplantation of bone marrow mononuclear cells (BMMNCs) into ischemic myocardium improves cardiac function. The objective of the present study was to evaluate the safety and feasibility of intramyocardial BMMNC transplantation into nongraftable areas in combination with off-pump coronary artery bypass grafting in patients with ischemic cardiomyopathy.
Five male patients with myocardial infarction lasting for more than 1 month and with nongraftable myocardium received autologous mononuclear cell transplantation during off-pump coronary artery bypass grafting. Autologous bone marrow was aspirated from the iliac crest. BMMNCs (mean 1.6, standard error [SE] 0.3 × 109) including CD34-positive cells (mean 6.8, SE 1.1 × 106) and AC133-positive cells (mean 3.1, SE 1.7 × 106) were injected into the nongraftable ischemic myocardium. Heart function was evaluated with the use of echocardiography, and myocardial perfusion was examined with single photon emission computed tomography technetium-99mTc sestamibi scans.
Two months after cell transplantation, the mean ejection fraction had increased by 7.4%, SE 1.9% (p = 0.016) compared with that before cell transplantation and off-pump coronary artery bypass grafting. The increase in ejection fraction was not correlated with the number of transplanted total mononuclear cells, CD34-positive cells and AC133-positive cells. Myocardial perfusion at the cell-transplanted area increased after cell transplantation and off-pump coronary artery bypass grafting. No arrhythmia was observed.
The present clinical study suggests that intramyocardial transplantation of autologous BMMNCs into the ischemic area during off-pump coronary artery bypass grafting is both feasible and safe and has beneficial effects on cardiac function.
PMCID: PMC2552943  PMID: 18815649

Results 1-7 (7)