Evidence map›Paper›PMID 38363250›Full record

ArticleCytotherapy2024

Scalable manufacture of therapeutic mesenchymal stromal cell products on customizable microcarriers in vertical wheel bioreactors that improve direct visualization, product harvest, and cost.

Andrew Haskell, Berkley P White, Robert E Rogers, Erin Goebel, Megan G Lopez, Andrew E Syvyk, Daniela A de Oliveira, Heather A Barreda, Joshua Benton, Oscar R Benavides and 9 more

Open access · hybridAbstract read
In one paragraph

Article in Cytotherapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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

19 authors at 2 institutions in 1 country.

Andrew HaskellDepartment of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
Berkley P WhiteDepartment of Biomedical Engineering, Texas A&M University, College Station, Texas, USA.
Robert E RogersDepartment of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
Erin GoebelDepartment of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA; Department of Biomedical Engineering, Texas A&M University, College Station, Texas, USA.
Megan G LopezDepartment of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
Andrew E SyvykNational Center for Therapeutics Manufacturing, Texas A&M University, College Station, Texas, USA.
Daniela A de OliveiraNational Center for Therapeutics Manufacturing, Texas A&M University, College Station, Texas, USA; Biological and Agricultural Engineering, Texas A&M University, College Station, Texas, USA.
Heather A BarredaDepartment of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
Joshua BentonDepartment of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
Oscar R BenavidesDepartment of Biomedical Engineering, Texas A&M University, College Station, Texas, USA.
Sujata DalalDepartment of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
EunHye BaeDepartment of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
Yu ZhangDepartment of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
Kristen MaitlandDepartment of Biomedical Engineering, Texas A&M University, College Station, Texas, USA; Imaging Program, Chan Zuckerberg Initiative, Redwood City, California, USA.
Zivko NikolovNational Center for Therapeutics Manufacturing, Texas A&M University, College Station, Texas, USA; Biological and Agricultural Engineering, Texas A&M University, College Station, Texas, USA.
Fei LiuDepartment of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
Ryang Hwa LeeDepartment of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA.
Roland KaunasDepartment of Biomedical Engineering, Texas A&M University, College Station, Texas, USA. Electronic address: rkaunas@tamu.edu.
Carl A GregoryDepartment of Cell Biology and Genetics, Texas A&M School of Medicine, Bryan, Texas, USA. Electronic address: cgregory@tamu.edu.
Texas A&M University · USChan Zuckerberg Initiative (United States) · US

Funding

Advanced Methods for Mimicking the Osteogenic Niche to Heal BoneR01AR066033 · NIAMS · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI GREGORY, CARL A. · 2014 to 2017
$1.3M
NIAMS NIH HHS R01 AR066033
6 · The paper itself

Abstract

BACKGROUND

aimsHuman mesenchymal stromal cells (hMSCs) and their secreted products show great promise for treatment of musculoskeletal injury and inflammatory or immune diseases. However, the path to clinical utilization is hampered by donor-tissue variation and the inability to manufacture clinically relevant yields of cells or their products in a cost-effective manner. Previously we described a method to produce chemically and mechanically customizable gelatin methacryloyl (GelMA) microcarriers for culture of hMSCs. Herein, we demonstrate scalable GelMA microcarrier-mediated expansion of induced pluripotent stem cell (iPSC)-derived hMSCs (ihMSCs) in 500 mL and 3L vertical wheel bioreactors, offering several advantages over conventional microcarrier and monolayer-based expansion strategies.

methodsHuman mesenchymal stromal cells derived from induced pluripotent cells were cultured on custom-made spherical gelatin methacryloyl microcarriers in single-use vertical wheel bioreactors (PBS Biotech). Cell-laden microcarriers were visualized using confocal microscopy and elastic light scattering methodologies. Cells were assayed for viability and differentiation potential in vitro by standard methods. Osteogenic cell matrix derived from cells was tested in vitro for osteogenic healing using a rodent calvarial defect assay. Immune modulation was assayed with an in vivo peritonitis model using Zymozan A.

resultsThe optical properties of GelMA microcarriers permit noninvasive visualization of cells with elastic light scattering modalities, and harvest of product is streamlined by microcarrier digestion. At volumes above 500 mL, the process is significantly more cost-effective than monolayer culture. Osteogenic cell matrix derived from ihMSCs expanded on GelMA microcarriers exhibited enhanced in vivo bone regenerative capacity when compared to bone morphogenic protein 2, and the ihMSCs exhibited superior immunosuppressive properties in vivo when compared to monolayer-generated ihMSCs.

conclusionsThese results indicate that the cell expansion strategy described here represents a superior approach for efficient generation, monitoring and harvest of therapeutic MSCs and their products.

Indexed as

Cell Culture TechniquesMesenchymal Stem CellsBioreactorsBone RegenerationCell DifferentiationCell ProliferationCells, CulturedHumansOsteogenesisbioreactorcell culturegelatin methacryloyl microcarriersmesenchymal stromal cellsstem cell manufacturestem cell therapy

Identifiers

PMID38363250
PMCPMC11057043
OpenAlexW4391849207

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.