Dataset Information

Infrapatellar fat pad-derived mesenchymal stem cell-based spheroids enhance their therapeutic efficacy to reverse synovitis and fat pad fibrosis.

ABSTRACT:

Background

To investigate the in vitro and in vivo anti-inflammatory/anti-fibrotic capacity of IFP-MSC manufactured as 3D spheroids. Our hypothesis is that IFP-MSC do not require prior cell priming to acquire a robust immunomodulatory phenotype in vitro in order to efficiently reverse synovitis and IFP fibrosis, and secondarily delay articular cartilage damage in vivo.

Methods

Human IFP-MSC immunophenotype, tripotentiality, and transcriptional profiles were assessed in 3D settings. Multiplex secretomes were assessed in IFP-MSC spheroids [Crude (non-immunoselected), CD146⁺ or CD146^- immunoselected cells] and compared with 2D cultures with and without prior inflammatory/fibrotic cell priming. Functionally, IFP-MSC spheroids were assessed for their immunopotency on human PBMC proliferation and their effect on stimulated synoviocytes with inflammation and fibrotic cues. The anti-inflammatory and anti-fibrotic spheroid properties were further evaluated in vivo in a rat model of acute synovitis/fat pad fibrosis.

Results

Spheroids enhanced IFP-MSC phenotypic, transcriptional, and secretory immunomodulatory profiles compared to 2D cultures. Further, CD146⁺ IFP-MSC spheroids showed enhanced secretory and transcriptional profiles; however, these attributes were not reflected in a superior capacity to suppress activated PBMC. This suggests that 3D culturing settings are sufficient to induce an enhanced immunomodulatory phenotype in both Crude and CD146-immunoselected IFP-MSC. Crude IFP-MSC spheroids modulated the molecular response of synoviocytes previously exposed to inflammatory cues. Therapeutically, IFP-MSC spheroids retained substance P degradation potential in vivo, while effectively inducing resolution of inflammation/fibrosis of the synovium and fat pad. Furthermore, their presence resulted in arrest of articular cartilage degradation in a rat model of progressive synovitis and fat pad fibrosis.

Conclusions

3D spheroids confer IFP-MSC a reproducible and enhanced immunomodulatory effect in vitro and in vivo, circumventing the requirement of non-compliant cell priming or selection before administration and thereby streamlining cell products manufacturing protocols.

SUBMITTER: Kouroupis D

PROVIDER: S-EPMC7792122 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Infrapatellar fat pad-derived mesenchymal stem cell-based spheroids enhance their therapeutic efficacy to reverse synovitis and fat pad fibrosis.

Kouroupis Dimitrios D Willman Melissa A MA Best Thomas M TM Kaplan Lee D LD Correa Diego D

Stem cell research & therapy 20210107 1

<h4>Background</h4>To investigate the in vitro and in vivo anti-inflammatory/anti-fibrotic capacity of IFP-MSC manufactured as 3D spheroids. Our hypothesis is that IFP-MSC do not require prior cell priming to acquire a robust immunomodulatory phenotype in vitro in order to efficiently reverse synovitis and IFP fibrosis, and secondarily delay articular cartilage damage in vivo.<h4>Methods</h4>Human IFP-MSC immunophenotype, tripotentiality, and transcriptional profiles were assessed in 3D settings ...[more]

PMID: 33413649

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Project description:BackgroundInterpretation of patellar ligament (PL) ultrasonography may be difficult, as hypoechoic or heterogenous echogenicity are common findings. Verifying suspected disease of equine PLs by histopathology is also problematic as descriptions of normal PL vascularity and histology are scarce. The current study describes the PL and infrapatellar fat pad (IFP) vascular pattern from computed tomography scans of barium perfused normal equine specimens (n = 8; age 10 days to 18 years), as well as routine histology to serve as a reference for future investigations into PL pathology and IFP disease.ResultsThe PLs received a bipolar blood supply. Vascular architecture consisted of numerous distinct longitudinal vessels with several horizontal connections, which branched into extensive latticeworks of smaller vessels throughout the ligaments. Several vascular connections between the PLs and the IFP were identified. One distinct longitudinal vessel was seen entering each of the IFP lobes at the distocranial aspect, branching extensively into lobar vascular networks which anastomosed by several horizontal branches at the mid portion of the IFP where the two lobes merge. Histologically, there were large variations in PL interfascicular endotenon thickness, vascularity and fatty infiltration; these parameters increased with age for the intermediate and medial PL. Areas of metaplastic tenocytes / chondroid metaplasia were identified in all investigated adult medial PLs; in 2/7 in the intermediate PL and in 4/7 in the lateral PL. The adult IFP consisted of white unilocular adipose tissue, organized in lobules separated by thin connective tissue septa increasing in thickness towards the periphery and the distocentral aspect.ConclusionsThe equine PLs and IFP are highly vascularized structures with ample vascular connections suggestive of crosstalk. This, together with the large variation in PL endotenon thickness, vascularity and fatty infiltration, should be taken into consideration when assessing potential PL histopathology as these changes increase with age and are found in horses without clinical signs of stifle disease. Metaplastic tenocytes / chondroid metaplasia should be considered a normal finding throughout the medial PL and is not age dependent. The role of the equine IFP in stifle disease has yet to be elucidated.

Project description:Background Infrapatellar fat pad (IPFP) quality has been implicated as a marker for predicting knee osteoarthritis (KOA); however, no valid quantification for subtle IPFP abnormalities has been established. Purpose To investigate whether MRI-based three-dimensional texture analysis of IPFP abnormalities could help predict incident radiographic KOA. Materials and Methods In this prospective nested case-control study, 690 participants whose knees were at risk for KOA were included from the Pivotal Osteoarthritis Initiative MRI Analyses incident osteoarthritis cohort. All knees had a Kellgren-Lawrence grade of 1 or less at baseline. During the 4-year follow-up, case participants were matched 1:1 to control participants, with incident radiographic KOA as the outcome. MRI scans were segmented at the incident time point of KOA (hereafter, P0), 1 year before P0 (hereafter, P-1), and baseline. MRI-based three-dimensional texture analysis was performed to extract IPFP texture features. Least absolute shrinkage and selection operator and multivariable logistic regressions were applied in the development cohort and evaluated in the test cohort. The area under the receiver operating characteristic curve (AUC) was used to evaluate the discriminative value of the clinical score, IPFP texture score, and MRI Osteoarthritis Knee Score. Results Participants were allocated to development (n = 500, 340 women; mean age, 60 years) and test (n = 190, 120 women; mean age, 61 years) cohorts. In both cohorts, IPFP texture scores (AUC ≥0.75 for all) showed greater discrimination than clinical scores (AUC ≤0.69 for all) at baseline, P-1, and P0, with significant differences in pairwise comparisons (P ≤ .002 for all). Greater predictive and concurrent validities of IPFP texture scores (AUC ≥0.75 for all) compared with MRI Osteoarthritis Knee Scores (AUC ≤0.66 for all) were also demonstrated (P < .001 for all). Conclusion MRI-based three-dimensional texture of the infrapatellar fat pad was associated with future development of knee osteoarthritis. ClinicalTrials.gov registration no.: NCT00080171 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Fischer in this issue.

Dataset Information

Infrapatellar fat pad-derived mesenchymal stem cell-based spheroids enhance their therapeutic efficacy to reverse synovitis and fat pad fibrosis.

Background

Methods

Results

Conclusions

Publications

Infrapatellar fat pad-derived mesenchymal stem cell-based spheroids enhance their therapeutic efficacy to reverse synovitis and fat pad fibrosis.

Similar Datasets

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