Evidence map›Paper›PMID 30881083›Full record

ArticleJournal of inflammation research2019

Alginate encapsulation for bupivacaine delivery and mesenchymal stromal cell immunomodulatory cotherapy.

Mollie S Davis, Ileana Marrero-Berrios, Isabel Perez, Charles P Rabolli, Palangat Radhakrishnan, Devasena Manchikalapati, Joseph Schianodicola, Hattiyangangadi Kamath, Rene S Schloss, Joel Yarmush

Open access · goldAbstract read
In one paragraph

Article in Journal of inflammation research, 2019. 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
2.6field-weighted citation impact, top 11% 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, 11 citations in OpenAlex.

  1. Article
  2. Article
  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

10 authors at 2 institutions in 2 countries.

Mollie S DavisDepartment of Biomedical Engineering, Rutgers University, Piscataway, NJ, USA, schloss@soemail.rutgers.edu.
Ileana Marrero-BerriosDepartment of Biomedical Engineering, Rutgers University, Piscataway, NJ, USA, schloss@soemail.rutgers.edu.
Isabel PerezDepartment of Biomedical Engineering, Rutgers University, Piscataway, NJ, USA, schloss@soemail.rutgers.edu.
Charles P RabolliDepartment of Biomedical Engineering, Rutgers University, Piscataway, NJ, USA, schloss@soemail.rutgers.edu.
Palangat RadhakrishnanDepartment of Anesthesiology, New York Methodist Hospital, Brooklyn, NY, USA.
Devasena ManchikalapatiDepartment of Anesthesiology, New York Methodist Hospital, Brooklyn, NY, USA.
Joseph SchianodicolaDepartment of Anesthesiology, New York Methodist Hospital, Brooklyn, NY, USA.
Hattiyangangadi KamathDepartment of Anesthesiology, New York Methodist Hospital, Brooklyn, NY, USA.
Rene S SchlossDepartment of Biomedical Engineering, Rutgers University, Piscataway, NJ, USA, schloss@soemail.rutgers.edu.
Joel YarmushDepartment of Anesthesiology, New York Methodist Hospital, Brooklyn, NY, USA.
NewYork–Presbyterian Brooklyn Methodist Hospital · USRutgers, The State University of New Jersey · US

Funding

X-RAY STRUCTURE OF RIFM PROTEIN FROM THE BIOSYNTHESIS PATHWAY OF THE ANSAMYCIN AP41RR012408 · NCRR · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI MARIUZZA, ROY A · 1998 to 2011
$32.2M
UMDNJ TRAINING GRANT IN BIOTECHNOLOGYT32GM008339 · NIGMS · RUTGERS THE ST UNIV OF NJ NEW BRUNSWICK · PI YARMUSH, MARTIN L · 1989 to 2019
$6.1M
NCRR NIH HHS P41 RR012408NIGMS NIH HHS T32 GM008339
6 · The paper itself

Abstract

purposeMesenchymal stromal cells (MSCs) are used to treat various inflammatory conditions. In parallel, to mitigate pain associated with inflammation, analgesics or opioids are prescribed, often with significant side effects. Local anesthetics (LAs) offer a promising alternative to these medications. However, their short duration and negative effects on anti-inflammatory MSCs have limited their therapeutic effectiveness. To mitigate these negative effects and to move toward developing a cotherapy, we engineered a sustained release bupivacaine alginate-liposomal construct that enables up to 4 days of LA release. By encapsulating MSC in alginate (eMSC), we demonstrate that we can further increase drug concentration to clinically relevant levels, without compromising eMSC viability or anti-inflammatory function. MATERIALS AND

methodsMSCs were freely cultured or encapsulated in alginate microspheres ± TNFα/IFN-γ and were left untreated or dosed with bolus, liposomal, or construct bupivacaine. After 24, 48, and 96 hours, the profiles were assessed to quantify secretory function associated with LA-MSC interactions. To approximate LA exposure over time, a MATLAB model was generated.

resultseMSCs secrete similar levels of IL-6 and prostaglandin E2 (PGE2) regardless of LA modality, whereas free MSCs secrete larger amounts of IL-6 and lower amounts of anti-inflammatory PGE2. Modeling the system indicated that higher doses of LA can be used in conjunction with eMSC while retaining eMSC viability and function. In general, eMSC treated with higher doses of LA secreted similar or higher levels of immunomodulatory cytokines.

conclusioneMSCs, but not free MSC, are protected from LA, regardless of LA modality. Increasing the LA concentration may promote longer and stronger pain mitigation while the protected eMSCs secrete similar, if not higher, immunomodulatory cytokine levels. Therefore, we have developed an approach, using eMSC and the LA construct that can potentially be used to reduce pain as well as improve MSC anti-inflammatory function.

Indexed as

drug diffusion modelencapsulated MSClocal anestheticsMSC cytokine secretion

Identifiers

PMID30881083
PMCPMC6419600
OpenAlexW2921085375

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.