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      KCI등재 SCI SCIE SCOPUS

      Optimal Dose and Timing of Umbilical Stem Cells Treatment in Pulmonary Arterial Hypertensive Rats

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      https://www.riss.kr/link?id=A103611157

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      다국어 초록 (Multilingual Abstract)

      Purpose: Pulmonary arterial hypertension (PAH) is a fatal disease which is characterized by an increase in pulmonary arterial pressureleading to increases in right ventricular afterload. Human umbilical cord blood derived-mesenchymal stem cells (hUCB-...

      Purpose: Pulmonary arterial hypertension (PAH) is a fatal disease which is characterized by an increase in pulmonary arterial pressureleading to increases in right ventricular afterload. Human umbilical cord blood derived-mesenchymal stem cells (hUCB-MSCs) administered via the jugular vein have been previously shown to improve PAH by reversal treatment. However, the effect of low dosageand transfusion timing of hUCB-MSCs on PAH has not yet been clearly established. Obviously, low dosage treatment can lead to a reduction in costs. This is the first study on early transfusion effect.
      Materials and Methods: This study was divided into two parts. The first part is an investigation of dose-dependent effect. hUCB-MSCs were administered into 3 groups of rats (UA: 3×106 cells, UB: 1.5×106 cells, UC: 3×105 cells) via the external jugular vein at week 1 after monocrotaline (MCT) injection. The second part is a search for optimal treatment timing in 3×105 cells dose of hUCB-MSCs administered at day 1 for UD group (low dose of hUCB-MSCs at day 1), at day 1 and week 1 for the UE group (dual transfusionof low dose of hUCB-MSCs at day 1 and week 1) and at 1 week for the UF group (reversal treatment of low dose hUCB-MSC at week 1) after MCT injection.
      Results: The administration of 3×105 hUCB-MSCs was as effective as the 3×106 dose in decreasing mean right ventricle (RV) pressureand pulmonary pathological changes. Early treatment with hUCB-MSCs improved mean RV pressure, pulmonary pathologicalchanges and heart collagen 3 protein expression levels in PAH.
      Conclusion: Low-dose early treatment of hUCB-MSCs is as effective as a high dose treatment of hUCB-MSCs in improving PAH although dual or reversal treatment is still more effective.

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      참고문헌 (Reference)

      1 Simonneau G, "Updated clinical classification of pulmonary hypertension" 62 (62): D34-D41, 2013

      2 Musina RA, "Umbilical cord blood mesenchymal stem cells" 143 : 127-131, 2007

      3 Le Blanc K, "Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells" 363 : 1439-1441, 2004

      4 Humbert M, "Treatment of pulmonary arterial hypertension" 351 : 1425-1436, 2004

      5 이혜련, "The Effect of Umbilical Cord Blood Derived Mesenchymal Stem Cells in Monocrotaline-induced Pulmonary Artery Hypertension Rats" 대한의학회 30 (30): 576-585, 2015

      6 Barczyk M, "Stem cell-based therapy in idiopathic pulmonary fibrosis" 11 : 598-620, 2015

      7 Ionescu L, "Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action" 303 : L967-L977, 2012

      8 Pierro M, "Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia" 68 : 475-484, 2013

      9 Zhao YD, "Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: efficacy of combined cell and eNOS gene therapy in established disease" 96 : 442-450, 2005

      10 Zhang WG, "Regulation of transplanted mesenchymal stem cells by the lung progenitor niche in rats with chronic obstructive pulmonary disease" 15 : 33-, 2014

      1 Simonneau G, "Updated clinical classification of pulmonary hypertension" 62 (62): D34-D41, 2013

      2 Musina RA, "Umbilical cord blood mesenchymal stem cells" 143 : 127-131, 2007

      3 Le Blanc K, "Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells" 363 : 1439-1441, 2004

      4 Humbert M, "Treatment of pulmonary arterial hypertension" 351 : 1425-1436, 2004

      5 이혜련, "The Effect of Umbilical Cord Blood Derived Mesenchymal Stem Cells in Monocrotaline-induced Pulmonary Artery Hypertension Rats" 대한의학회 30 (30): 576-585, 2015

      6 Barczyk M, "Stem cell-based therapy in idiopathic pulmonary fibrosis" 11 : 598-620, 2015

      7 Ionescu L, "Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action" 303 : L967-L977, 2012

      8 Pierro M, "Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia" 68 : 475-484, 2013

      9 Zhao YD, "Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: efficacy of combined cell and eNOS gene therapy in established disease" 96 : 442-450, 2005

      10 Zhang WG, "Regulation of transplanted mesenchymal stem cells by the lung progenitor niche in rats with chronic obstructive pulmonary disease" 15 : 33-, 2014

      11 Mei SH, "Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1" 4 : e269-, 2007

      12 Gnecchi M, "Paracrine mechanisms in adult stem cell signaling and therapy" 103 : 1204-1219, 2008

      13 Rabinovitch M, "Molecular pathogenesis of pulmonary arterial hypertension" 122 : 4306-4313, 2012

      14 Chang YS, "Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1dose-escalation clinical trial" 164 : 966-972, 2014

      15 Hansmann G, "Mesenchymal stem cell-mediated reversal of bronchopulmonary dysplasia and associated pulmonary hypertension" 2 : 170-181, 2012

      16 Ortiz LA, "Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects" 100 : 8407-8411, 2003

      17 Sitbon O, "Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival" 40 : 780-788, 2002

      18 Souidi N, "Ischemia-reperfusion injury: beneficial effects of mesenchymal stromal cells" 18 : 34-43, 2013

      19 Baber SR, "Intratracheal mesenchymal stem cell administration attenuates monocrotaline-induced pulmonary hypertension and endothelial dysfunction" 292 : H1120-H1128, 2007

      20 Price LC, "Inflammation in pulmonary arterial hypertension" 141 : 210-221, 2012

      21 Huertas A, "Immune dysregulation and endothelial dysfunction in pulmonary arterial hypertension: a complex interplay" 129 : 1332-1340, 2014

      22 Polchert D, "IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease" 38 : 1745-1755, 2008

      23 Li J, "Human umbilical cord mesenchymal stem cells reduce systemic inflammation and attenuate LPSinduced acute lung injury in rats" 9 : 33-, 2012

      24 Xue J, "Gene-modified mesenchymal stem cells protect against radiation-induced lung injury" 21 : 456-465, 2013

      25 Lee HR, "Effects of octylphenol on the expression of cell cycle-related genes and the growth of mesenchymal stem cells derived from human umbilical cord blood" 33 : 221-226, 2014

      26 Liu CH, "Cytokine interactions in mesenchymal stem cells from cord blood" 32 : 270-279, 2005

      27 Lee JW, "Concise review: mesenchymal stem cells for acute lung injury:role of paracrine soluble factors" 29 : 913-919, 2011

      28 Weiss DJ, "Concise review: current status of stem cells and regenerative medicine in lung biology and diseases" 32 : 16-25, 2014

      29 Kern S, "Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue" 24 : 1294-1301, 2006

      30 김관창, "Changes in Caspase-3, Bcl-2, Interleukine-6, Tumor Necrosis Factor-α and Vascular Endothelial Growth Factor Gene Expressions after Human Umbilical Cord Blood Derived Mesenchymal Stem Cells Transfusion in Pulmonary Hypertension Rat Models" 대한심장학회 46 (46): 79-92, 2016

      31 Couri CE, "C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus" 301 : 1573-1579, 2009

      32 Jin Z, "Biological effects and mechanisms of action of mesenchymal stem cell therapy in chronic obstructive pulmonary disease" 43 : 303-310, 2015

      33 Gitelman SE, "Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus" 302 : 624-625, 2009

      34 Umar S, "Allogenic stem cell therapy improves right ventricular function by improving lung pathology in rats with pulmonary hypertension" 297 : H1606-H1616, 2009

      35 van Haaften T, "Airway delivery of mesenchymal stem cells prevents arrested alveolar growth in neonatal lung injury in rats" 180 : 1131-1142, 2009

      36 Wannemuehler TJ, "Advances in mesenchymal stem cell research in sepsis" 173 : 113-126, 2012

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      2023 평가예정 해외DB학술지평가 신청대상 (해외등재 학술지 평가)
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      2011-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2009-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2007-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2005-05-31 학술지등록 한글명 : Yonsei Medical Journal
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      2005-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2002-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2000-01-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 1.42 0.3 0.99
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.83 0.72 0.546 0.08
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