Optimal dose and timing of umbilical stem cells treatment in pulmonary arterial hypertensive rats

Hyeryon Lee, Kwan Chang Kim, Soo Jin Choi, Young Mi Hong

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Purpose: Pulmonary arterial hypertension (PAH) is a fatal disease which is characterized by an increase in pulmonary arterial pressure leading 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 dosage and 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 transfusion of 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) pressure and pulmonary pathological changes. Early treatment with hUCB-MSCs improved mean RV pressure, pulmonary pathological changes 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.

Original languageEnglish
Pages (from-to)570-580
Number of pages11
JournalYonsei Medical Journal
Volume58
Issue number3
DOIs
StatePublished - May 2017

Bibliographical note

Funding Information:
The authors gratefully acknowledge the support provided by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2013 R1A1A3004619), and intramural research promotion grants from Ewha Womans University School of Medicine.

Publisher Copyright:
© Yonsei University College of Medicine 2017.

Keywords

  • Mesenchymal stem cell
  • Prophylaxis
  • Pulmonary hypertension

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