Transcriptional profiling of young and old mesenchymal stem cells in response to oxygen deprivation and reparability of the infarcted myocardium

Shujia Jiang, Husnain Kh Haider, Rafeeq P.H. Ahmed, Niagara M. Idris, Asmat Salim, Muhammad Ashraf

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Most clinical studies have used autologous bone marrow (BM) stem cells for myocardial regeneration in elderly patients. We hypothesize that aging impairs the survival and differentiation potential of BM stem cells thus limiting their therapeutic efficacy. BM-derived MSCs from young (YngMSCs; 8-12 weeks) and old (OldMSCs; 24-26 months) rats were purified and assessed for their responsiveness to anoxia and reparability of infarcted heart. Higher expression of angiogenic growth factors was observed by YngMSCs under anoxia as compared to OldMSCs, cultured either alone or in co-culture (Co-oldMSCs) with YngMSCs. Likewise, YngMSCs were more tolerant to apoptotic stimuli and showed higher ability to form tubular structures during in vitro Matrigel assay as compared to OldMSCs and Co-oldMSCs with a possible role of p21 and p27 as contributory survival factors. For in vivo studies, acute myocardial infarction model was developed in Fischer-344 rats (n = 38). The animals were grouped to receive 70 μl basal DMEM without cells (group 1) or containing 2 × 106 YngMSCs (PKH67 labeled; group 2) or OldMSCs (PKH26 labeled; group 3) and mixture of YngMSCs + OldMSCs (1 × 106 cells each; group 4). Histological studies revealed that by day 7, YngMSCs showed elongated morphology with orientation similar to the host muscle architecture. Electron microscopy and confocal imaging after fluorescent immunostaining showed superior angiomyogenic potential of YngMSCs. Echocardiography showed significantly preserved heart function indices in the animals transplanted with YngMSCs. Aging impairs the responsiveness of OldMSCs to anoxia and their differentiation potential. YngMSCs fail to alter the survival of OldMSCs under in vitro as well as in vivo conditions. It is therefore concluded that transplantation of stem cells from young donors would be a better option for heart cell therapy in future clinical studies.

Original languageEnglish (US)
Pages (from-to)582-596
Number of pages15
JournalJournal of molecular and cellular cardiology
Volume44
Issue number3
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

Fingerprint

Mesenchymal Stromal Cells
Myocardium
Oxygen
Bone Marrow Cells
Stem Cells
Survival
Angiogenesis Inducing Agents
Inbred F344 Rats
Stem Cell Transplantation
Cell- and Tissue-Based Therapy
Coculture Techniques
Echocardiography
Regeneration
Intercellular Signaling Peptides and Proteins
Electron Microscopy
Bone Marrow
Myocardial Infarction
Muscles
Hypoxia
Clinical Studies

Keywords

  • Aging
  • Angiogenesis
  • Myocardial infarction
  • Myocardium
  • Myogenesis
  • Stem cells
  • Transplantation

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Transcriptional profiling of young and old mesenchymal stem cells in response to oxygen deprivation and reparability of the infarcted myocardium. / Jiang, Shujia; Kh Haider, Husnain; Ahmed, Rafeeq P.H.; Idris, Niagara M.; Salim, Asmat; Ashraf, Muhammad.

In: Journal of molecular and cellular cardiology, Vol. 44, No. 3, 01.03.2008, p. 582-596.

Research output: Contribution to journalArticle

@article{f61dbe6826aa448aa8445e85b6e95b3f,
title = "Transcriptional profiling of young and old mesenchymal stem cells in response to oxygen deprivation and reparability of the infarcted myocardium",
abstract = "Most clinical studies have used autologous bone marrow (BM) stem cells for myocardial regeneration in elderly patients. We hypothesize that aging impairs the survival and differentiation potential of BM stem cells thus limiting their therapeutic efficacy. BM-derived MSCs from young (YngMSCs; 8-12 weeks) and old (OldMSCs; 24-26 months) rats were purified and assessed for their responsiveness to anoxia and reparability of infarcted heart. Higher expression of angiogenic growth factors was observed by YngMSCs under anoxia as compared to OldMSCs, cultured either alone or in co-culture (Co-oldMSCs) with YngMSCs. Likewise, YngMSCs were more tolerant to apoptotic stimuli and showed higher ability to form tubular structures during in vitro Matrigel assay as compared to OldMSCs and Co-oldMSCs with a possible role of p21 and p27 as contributory survival factors. For in vivo studies, acute myocardial infarction model was developed in Fischer-344 rats (n = 38). The animals were grouped to receive 70 μl basal DMEM without cells (group 1) or containing 2 × 106 YngMSCs (PKH67 labeled; group 2) or OldMSCs (PKH26 labeled; group 3) and mixture of YngMSCs + OldMSCs (1 × 106 cells each; group 4). Histological studies revealed that by day 7, YngMSCs showed elongated morphology with orientation similar to the host muscle architecture. Electron microscopy and confocal imaging after fluorescent immunostaining showed superior angiomyogenic potential of YngMSCs. Echocardiography showed significantly preserved heart function indices in the animals transplanted with YngMSCs. Aging impairs the responsiveness of OldMSCs to anoxia and their differentiation potential. YngMSCs fail to alter the survival of OldMSCs under in vitro as well as in vivo conditions. It is therefore concluded that transplantation of stem cells from young donors would be a better option for heart cell therapy in future clinical studies.",
keywords = "Aging, Angiogenesis, Myocardial infarction, Myocardium, Myogenesis, Stem cells, Transplantation",
author = "Shujia Jiang and {Kh Haider}, Husnain and Ahmed, {Rafeeq P.H.} and Idris, {Niagara M.} and Asmat Salim and Muhammad Ashraf",
year = "2008",
month = "3",
day = "1",
doi = "10.1016/j.yjmcc.2007.11.014",
language = "English (US)",
volume = "44",
pages = "582--596",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Transcriptional profiling of young and old mesenchymal stem cells in response to oxygen deprivation and reparability of the infarcted myocardium

AU - Jiang, Shujia

AU - Kh Haider, Husnain

AU - Ahmed, Rafeeq P.H.

AU - Idris, Niagara M.

AU - Salim, Asmat

AU - Ashraf, Muhammad

PY - 2008/3/1

Y1 - 2008/3/1

N2 - Most clinical studies have used autologous bone marrow (BM) stem cells for myocardial regeneration in elderly patients. We hypothesize that aging impairs the survival and differentiation potential of BM stem cells thus limiting their therapeutic efficacy. BM-derived MSCs from young (YngMSCs; 8-12 weeks) and old (OldMSCs; 24-26 months) rats were purified and assessed for their responsiveness to anoxia and reparability of infarcted heart. Higher expression of angiogenic growth factors was observed by YngMSCs under anoxia as compared to OldMSCs, cultured either alone or in co-culture (Co-oldMSCs) with YngMSCs. Likewise, YngMSCs were more tolerant to apoptotic stimuli and showed higher ability to form tubular structures during in vitro Matrigel assay as compared to OldMSCs and Co-oldMSCs with a possible role of p21 and p27 as contributory survival factors. For in vivo studies, acute myocardial infarction model was developed in Fischer-344 rats (n = 38). The animals were grouped to receive 70 μl basal DMEM without cells (group 1) or containing 2 × 106 YngMSCs (PKH67 labeled; group 2) or OldMSCs (PKH26 labeled; group 3) and mixture of YngMSCs + OldMSCs (1 × 106 cells each; group 4). Histological studies revealed that by day 7, YngMSCs showed elongated morphology with orientation similar to the host muscle architecture. Electron microscopy and confocal imaging after fluorescent immunostaining showed superior angiomyogenic potential of YngMSCs. Echocardiography showed significantly preserved heart function indices in the animals transplanted with YngMSCs. Aging impairs the responsiveness of OldMSCs to anoxia and their differentiation potential. YngMSCs fail to alter the survival of OldMSCs under in vitro as well as in vivo conditions. It is therefore concluded that transplantation of stem cells from young donors would be a better option for heart cell therapy in future clinical studies.

AB - Most clinical studies have used autologous bone marrow (BM) stem cells for myocardial regeneration in elderly patients. We hypothesize that aging impairs the survival and differentiation potential of BM stem cells thus limiting their therapeutic efficacy. BM-derived MSCs from young (YngMSCs; 8-12 weeks) and old (OldMSCs; 24-26 months) rats were purified and assessed for their responsiveness to anoxia and reparability of infarcted heart. Higher expression of angiogenic growth factors was observed by YngMSCs under anoxia as compared to OldMSCs, cultured either alone or in co-culture (Co-oldMSCs) with YngMSCs. Likewise, YngMSCs were more tolerant to apoptotic stimuli and showed higher ability to form tubular structures during in vitro Matrigel assay as compared to OldMSCs and Co-oldMSCs with a possible role of p21 and p27 as contributory survival factors. For in vivo studies, acute myocardial infarction model was developed in Fischer-344 rats (n = 38). The animals were grouped to receive 70 μl basal DMEM without cells (group 1) or containing 2 × 106 YngMSCs (PKH67 labeled; group 2) or OldMSCs (PKH26 labeled; group 3) and mixture of YngMSCs + OldMSCs (1 × 106 cells each; group 4). Histological studies revealed that by day 7, YngMSCs showed elongated morphology with orientation similar to the host muscle architecture. Electron microscopy and confocal imaging after fluorescent immunostaining showed superior angiomyogenic potential of YngMSCs. Echocardiography showed significantly preserved heart function indices in the animals transplanted with YngMSCs. Aging impairs the responsiveness of OldMSCs to anoxia and their differentiation potential. YngMSCs fail to alter the survival of OldMSCs under in vitro as well as in vivo conditions. It is therefore concluded that transplantation of stem cells from young donors would be a better option for heart cell therapy in future clinical studies.

KW - Aging

KW - Angiogenesis

KW - Myocardial infarction

KW - Myocardium

KW - Myogenesis

KW - Stem cells

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=40649113341&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40649113341&partnerID=8YFLogxK

U2 - 10.1016/j.yjmcc.2007.11.014

DO - 10.1016/j.yjmcc.2007.11.014

M3 - Article

VL - 44

SP - 582

EP - 596

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

SN - 0022-2828

IS - 3

ER -