Proteoglycan 4 is present within the dura mater and produced by mesenchymal progenitor cells

Mudigonda, Sathvika; Shah, Sophia; Das, Nabangshu; Corpuz, Jessica May; Ninkovic, Nicoletta; Al-Jezani, Nedaa; Underhill, T. Michael; Salo, Paul; Mitha, Alim P.; Lyons, Frank; Cho, Roger; Schmidt, Tannin A.; Dufour, Antoine; Krawetz, Roman

doi:10.1007/s00441-022-03647-4

Cited by 4 publications

(2 citation statements)

References 67 publications

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“…Cells of a given phenotype were identified and quantitated using the TissueQuest software (TissueGnostics), with cut-off values determined relative to the negative controls (non-stained and secondary alone controls). Gating and quantification of single/double positive cells were undertaken using these thresholds [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

Mesenchymal progenitor cells from non-inflamed versus inflamed synovium post-ACL injury present with distinct phenotypes and cartilage regeneration capacity

et al. 2023

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Background Osteoarthritis (OA) is a chronic debilitating disease impacting a significant percentage of the global population. While there are numerous surgical and non-invasive interventions that can postpone joint replacement, there are no current treatments which can reverse the joint damage occurring during the pathogenesis of the disease. While many groups are investigating the use of stem cell therapies in the treatment of OA, we still don’t have a clear understanding of the role of these cells in the body, including heterogeneity of tissue resident adult mesenchymal progenitor cells (MPCs). Methods In the current study, we examined MPCs from the synovium and individuals with or without a traumatic knee joint injury and explored the chondrogenic differentiation capacity of these MPCs in vitro and in vivo. Results We found that there is heterogeneity of MPCs with the adult synovium and distinct sub-populations of MPCs and the abundancy of these sub-populations change with joint injury. Furthermore, only some of these sub-populations have the ability to effect cartilage repair in vivo. Using an unbiased proteomics approach, we were able to identify cell surface markers that identify this pro-chondrogenic MPC population in normal and injured joints, specifically CD82LowCD59+ synovial MPCs have robust cartilage regenerative properties in vivo. Conclusions The results of this study clearly show that cells within the adult human joint can impact cartilage repair and that these sub-populations exist within joints that have undergone a traumatic joint injury. Therefore, these populations can be exploited for the treatment of cartilage injuries and OA in future clinical trials.

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Section: Methodsmentioning

confidence: 99%

Mesenchymal progenitor cells from non-inflamed versus inflamed synovium post-ACL injury present with distinct phenotypes and cartilage regeneration capacity

et al. 2023

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“…We have also used this mouse to determine that MPCs in the epidural fat and dura express Prx1. [13,15,28,29] We further employed this lineage tracking method on a p21 −/− background to identify if there was a change in behavior of these MPCs in vivo with the deletion of p21.…”

Section: Introductionmentioning

confidence: 99%

Prx1⁺ MPCs Accumulate in the Dura Mater of Wild‐Type and p21^−/− Mice Followed by a Specific Reduction in p21^−/− Dural MPCs

et al. 2022

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during revision surgeries for patients with epidural fibrosis. [2] Patients who experience incidental durotomies suffer from worse post-operative clinical results, such as a higher rate of reoperations, increased back pain, and reduced working ability. [3] However, appropriate treatment can diminish long-term sequelae post-dural injury. The use of synthetic and biological grafts to treat insults to the dura mater began in the 20th century, including polymer sheets, autografts, allografts, and even xenografts. [4] To date however, a successful graft which mimics perfectly the collagen fiber arrangement and accordingly the biomechanical properties of the dura mater remains elusive.Given loss of epidural fat can promote fibrosis in the vertebral environment, efforts have been made to re-introduce epidural fat into the vertebral column including engineered fat from adiposederived mesenchymal progenitor cells (MPCs), [1] injectable extracellular matrices, [5][6][7] and fat grafting. [6,[8][9][10] Attempts at preventing epidural fibrosis thus protecting the dura mater have also been made using biomaterials like DuraGen, [11] and injection of nonsteroidal anti-inflammatory drugs to re-balance the microenvironment to promote healing. [12] Regardless of the multiple different techniques being explored, no treatment exists that has gained wide clinical acceptance to prevent epidural fibrosis. Epidural fat contains a population of mesenchymal progenitor cells (MPCs), and this study explores the behavior of these cells on the adjacent dura mater during growth and in response toinjury in a p21 knockout mouse model. p21 −/− mice are known to have increased cell proliferation and enhanced tissue regeneration post-injury. Therefore, it is hypothesized that the process by which epidural fat MPCs maintain the dura mater can be accelerated in p21 −/− mice. Using a Prx1 lineage tracing mouse model, the epidural fat MPCs are found to increase in the dura mater over time in both C57BL/6 (p21 +/+ ) and p21 −/− mice; however, by 3 weeks post-tamoxifen induction, few MPCs are observed in p21 −/− mice. These endogenous MPCs also localize to dural injuries in both mouse strains, with MPCs in p21 −/− mice demonstrating increased proliferation. When epidural fat MPCs derived from p21 −/− mice are transplanted into dural injuries in C57BL/6 mice, these MPCs are found in the injury site. It is demonstrated that epidural fat MPCs play a role in dural tissue maintenance and are able to directly contribute to dural injury repair. This suggests that these MPCs have the potential to treat injuries and/or pathologies in tissues surrounding the spinal cord.

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Role of epidural fat in the local milieu: what we know and what we don’t

Liu,

Wang,

et al. 2024

Connective Tissue Research

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Proteoglycan 4 is present within the dura mater and produced by mesenchymal progenitor cells

Cited by 4 publications

References 67 publications

Mesenchymal progenitor cells from non-inflamed versus inflamed synovium post-ACL injury present with distinct phenotypes and cartilage regeneration capacity

Mesenchymal progenitor cells from non-inflamed versus inflamed synovium post-ACL injury present with distinct phenotypes and cartilage regeneration capacity

Prx1⁺ MPCs Accumulate in the Dura Mater of Wild‐Type and p21^−/− Mice Followed by a Specific Reduction in p21^−/− Dural MPCs

Role of epidural fat in the local milieu: what we know and what we don’t

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Proteoglycan 4 is present within the dura mater and produced by mesenchymal progenitor cells

Cited by 4 publications

References 67 publications

Mesenchymal progenitor cells from non-inflamed versus inflamed synovium post-ACL injury present with distinct phenotypes and cartilage regeneration capacity

Mesenchymal progenitor cells from non-inflamed versus inflamed synovium post-ACL injury present with distinct phenotypes and cartilage regeneration capacity

Prx1+ MPCs Accumulate in the Dura Mater of Wild‐Type and p21−/− Mice Followed by a Specific Reduction in p21−/− Dural MPCs

Role of epidural fat in the local milieu: what we know and what we don’t

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Prx1⁺ MPCs Accumulate in the Dura Mater of Wild‐Type and p21^−/− Mice Followed by a Specific Reduction in p21^−/− Dural MPCs