Evidence map›Paper›PMID 25889271›Full record

ArticleStem cell research & therapy2015

Therapeutic potential of ixmyelocel-T, an expanded autologous multicellular therapy for treatment of ischemic cardiovascular diseases.

Kelly J Ledford, Nikki Murphy, Frank Zeigler, Ronnda L Bartel, Ross Tubo

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.0field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Review
  3. Mesenchymal Stem Cell-Based Therapy for Cardiovascular Disease: Progress and Challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2018
    Review
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Kelly J LedfordAastrom Biosciences, Domino's Farms, Lobby K 24 Frank Lloyd Wright Drive, Ann Arbor, MI, 48105, USA. kledford@aastrom.com.
Nikki MurphyAastrom Biosciences, Domino's Farms, Lobby K 24 Frank Lloyd Wright Drive, Ann Arbor, MI, 48105, USA. emurphy@aastrom.com.
Frank ZeiglerAastrom Biosciences, Domino's Farms, Lobby K 24 Frank Lloyd Wright Drive, Ann Arbor, MI, 48105, USA. frankthescientist@gmail.com.
Ronnda L BartelAastrom Biosciences, Domino's Farms, Lobby K 24 Frank Lloyd Wright Drive, Ann Arbor, MI, 48105, USA. ronnda@me.com.
Ross TuboAastrom Biosciences, Domino's Farms, Lobby K 24 Frank Lloyd Wright Drive, Ann Arbor, MI, 48105, USA. rtubo@vcel.com.
Aastrom Biosciences (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionBone marrow derived cellular therapies are an emerging approach to promoting therapeutic angiogenesis in ischemic cardiovascular disease. However, the percentage of regenerative cells in bone marrow mononuclear cells (BMMNCs) is small, and large amounts of BMMNCs are required. Ixmyelocel-T, an expanded autologous multicellular therapy, is manufactured from a small sample of bone marrow aspirate. Ixmyelocel-T contains expanded populations of mesenchymal stromal cells (MSCs) and M2-like macrophages, as well as many of the CD45+ cells found in the bone marrow. It is hypothesized that this expanded multi-cellular therapy would induce angiogenesis and endothelial repair.

methodsA rat model of hind limb ischemia was used to determine the effects of ixmyelocel-T on blood flow recovery. To further determine the effects on endothelial cells, ixmyelocel-T was co-cultured with human umbilical vein endothelial cells (HUVEC) in non-contacting Transwell® inserts.

resultsCo-culture of HUVECs with ixmyelocel-T resulted secretion of a variety of pro-angiogenic factors. HUVECs stimulated by ixmyelocel-T exhibited enhanced migration, proliferation, and branch formation. Ixmyelocel-T co-culture also resulted in increased endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) production. In tumor necrosis factor alpha (TNFα)-stimulated HUVECs, ixmyelocel-T co-culture decreased apoptosis and reactive oxygen species generation, increased super oxide dismutase activity, and decreased nuclear factor kappa B (NFκB) activation. Treatment with ixmyelocel-T in a rat model of hind limb ischemia resulted in significantly increased blood flow perfusion and capillary density, gene expression and plasma levels of the anti-inflammatory cytokine interleukin (IL)-10, plasma nitrates, plasma platelet-derived growth factor (PDGF)-BB, vascular endothelial growth factor (VEGF) expression, and significantly decreased plasma thiobarbituric acid reactive substances (TBARS).

conclusionsThis work demonstrates that ixmyelocel-T interacts with endothelial cells in a paracrine manner, resulting in angiogenesis and endothelial protection. This data suggests that ixmyelocel-T could be useful for promoting of angiogenesis and tissue repair in ischemic cardiovascular diseases. In conclusion, ixmyelocel-T therapy may provide a new aspect of therapeutic angiogenesis in this patient population where expanded populations of regenerative cells might be required.

Indexed as

Bone Marrow TransplantationMesenchymal Stem Cell TransplantationAnimalsApoptosisBecaplerminBone Marrow CellsCell- and Tissue-Based TherapyCell ProliferationCells, CulturedCoculture TechniquesDisease Models, AnimalEnzyme ActivationHindlimbHumansHuman Umbilical Vein Endothelial CellsInterleukin-10BecaplerminInterleukin-10Leukocyte Common AntigensNF-kappa BNitratesNitric OxideNitric Oxide Synthase Type IIIProto-Oncogene Proteins c-sisReactive Oxygen SpeciesSuperoxide DismutaseThiobarbituric Acid Reactive SubstancesTumor Necrosis Factor-alphaVascular Endothelial Growth Factor Avascular endothelial growth factor A, rat

Identifiers

PMID25889271
PMCPMC4413547
OpenAlexW2099304911

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.