Enhancing Retention of Human Bone Marrow Mesenchymal Stem Cells with Prosurvival Factors Promotes Angiogenesis in a Mouse Model of Limb Ischemia

Elizabeth Cortez-Toledo, Melanie Rose, Emmanuel Agu, Heather Dahlenburg, Wei Yao, Jan Nolta, Ping Zhou

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Mesenchymal stem/stromal cells (MSCs) offer great promise in the treatment of ischemic injuries, including stroke, heart infarction, and limb ischemia. However, poor cell survival after transplantation remains a major obstacle to achieve effective MSC therapies. To improve cell survival and retention, we transplanted human bone marrow MSCs with or without a specific prosurvival factor (PSF) cocktail consisting of IGF1, Bcl-XL, a caspase inhibitor, a mitochondrial pathway inhibitor, and Matrigel into the limbs of immune deficient mice, after induction of hindlimb ischemia. The PSF markedly prolonged the retention of the MSCs in the ischemic limb muscles as demonstrated by bioluminescence imaging. Using microcomputed tomography to image the limb muscle vasculature in the mice 9 weeks after the transplantation, we found that the mice transplanted with MSCs without PSF did not show a significant increase in the blood vessels in the ischemic limb compared with the nontransplanted control mice. In contrast, the mice transplanted with MSCs plus PSF showed a significant increase in the blood vessels, especially the larger and branching vessels, in the ischemic limb compared with the control mice that did not receive MSCs. Thus, we demonstrated that prolonged retention of MSCs using PSF effectively promoted angiogenesis in ischemic animal limbs. This study highlights the importance of enhancing cell survival in the development of effective MSC therapies to treat vascular diseases.

Original languageEnglish (US)
Pages (from-to)114-119
Number of pages6
JournalStem Cells and Development
Volume28
Issue number2
DOIs
StatePublished - Jan 15 2019

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Angiogenesis Inducing Agents
Mesenchymal Stromal Cells
Ischemia
Extremities
Bone Marrow
Cell Survival
Cell- and Tissue-Based Therapy
Blood Vessels
Transplantation
X-Ray Microtomography
Muscles
Caspase Inhibitors

Keywords

  • engraftment
  • ischemia
  • MSCs
  • prosurvival
  • vasculature

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

Cite this

Enhancing Retention of Human Bone Marrow Mesenchymal Stem Cells with Prosurvival Factors Promotes Angiogenesis in a Mouse Model of Limb Ischemia. / Cortez-Toledo, Elizabeth; Rose, Melanie; Agu, Emmanuel; Dahlenburg, Heather; Yao, Wei; Nolta, Jan; Zhou, Ping.

In: Stem Cells and Development, Vol. 28, No. 2, 15.01.2019, p. 114-119.

Research output: Contribution to journalArticle

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