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Erythrocyte removal from bone marrow aspirate concentrate improves efficacy as intra-articular cellular therapy in a rodent osteoarthritis model.


ABSTRACT:

Background

Despite the high prevalence of osteoarthritis (OA), there remains a need for additional therapeutic options. Cellular therapies with minimally manipulated cells such as bone marrow aspirate concentrates (BMAC) are increasingly popular in the U.S. but clear-cut evidence of efficacy has not been established. In theory, BMAC injections provide a source of stromal cells to stimulate healing in OA and ligamentous injuries; however, BMAC injections are also often associated with inflammation, short-term pain, and mobility impairment. Given that blood is known to trigger inflammation in joints, we hypothesized that removing erythrocytes [red blood cells (RBCs)] from BMAC preparations prior to intra-articular injection would improve efficacy for OA treatment.

Methods

To test this hypothesis, BMAC was collected from the bone marrow of mice. Three treatment groups were pursued: (I) untreated; (II) BMAC; or (III) BMAC depleted of RBCs by lysis. Product was injected into the femorotibial joint of mice 7 days after OA had been induced by destabilization of the medial meniscus (DMM). To assess the impact of treatment on joint function, individual cage monitoring (ANY-mazeTM) and Digigait treadmill-based analyses were performed over 4 weeks. At study completion, joint histopathology was assessed and immune transcriptomes within joint tissues were compared using a species-specific NanoString panel.

Results

Significant improvements in activity, gait parameters, and histology scores were seen in animals receiving RBC-depleted BMAC compared to untreated mice; animals treated with non-depleted BMAC did not demonstrate this same extent of consistent significant improvement. Transcriptomic analysis of joint tissues revealed significant upregulation of key anti-inflammatory genes, including interleukin-1 receptor antagonist (IRAP), in mice treated with RBC-depleted BMAC compared to animals treated with non-RBC depleted BMAC.

Conclusions

These findings indicate that RBC depletion in BMAC prior to intra-articular injection improves treatment efficacy and reduces joint inflammation compared to BMAC.

SUBMITTER: Pezzanite LM 

PROVIDER: S-EPMC10316095 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Erythrocyte removal from bone marrow aspirate concentrate improves efficacy as intra-articular cellular therapy in a rodent osteoarthritis model.

Pezzanite Lynn M LM   Timkovich Ariel E AE   Sikes Katie J KJ   Chow Lyndah L   Hendrickson Dean A DA   Becker Jordyn R JR   Webster Aaron A   Santangelo Kelly S KS   Dow Steven S  

Annals of translational medicine 20230525 9


<h4>Background</h4>Despite the high prevalence of osteoarthritis (OA), there remains a need for additional therapeutic options. Cellular therapies with minimally manipulated cells such as bone marrow aspirate concentrates (BMAC) are increasingly popular in the U.S. but clear-cut evidence of efficacy has not been established. In theory, BMAC injections provide a source of stromal cells to stimulate healing in OA and ligamentous injuries; however, BMAC injections are also often associated with inf  ...[more]

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