Tumor Formation of Adult Stem Cell Transplants in Rodent Arthritic Joints

Chapelin, Fanny; Khurana, Aman; Moneeb, Mohammad; Hazard, Florette K.; Chan, Chun Fai Ray; Nejadnik, Hossein; Gratzinger, Dita; Messing, Solomon; Erdmann, Jason; Gaur, Amitabh

doi:10.1007/s11307-018-1218-7

Cited by 14 publications

(10 citation statements)

References 60 publications

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“…The safety of MSCs in human therapies has been well-demonstrated with no major toxicity. The possibility of excess immunosuppression and tumor transformation was noted in experimental models of arthritis treated with MSCs, although none was recorded in human studies ( 203 ). A milieu of chronic inflammation is associated with autoimmune diseases, and such a milieu could affect the functions of MSCs ( 7 ).…”

Section: Discussionmentioning

confidence: 99%

Multipotent Mesenchymal Stromal Cells in Rheumatoid Arthritis and Systemic Lupus Erythematosus; From a Leading Role in Pathogenesis to Potential Therapeutic Saviors?

et al. 2021

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The pathogenesis of the autoimmune rheumatological diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is complex with the involvement of several immune cell populations spanning both innate and adaptive immunity including different T-lymphocyte subsets and monocyte/macrophage lineage cells. Despite therapeutic advances in RA and SLE, some patients have persistent and stubbornly refractory disease. Herein, we discuss stromal cells' dual role, including multipotent mesenchymal stromal cells (MSCs) also used to be known as mesenchymal stem cells as potential protagonists in RA and SLE pathology and as potential therapeutic vehicles. Joint MSCs from different niches may exhibit prominent pro-inflammatory effects in experimental RA models directly contributing to cartilage damage. These stromal cells may also be key regulators of the immune system in SLE. Despite these pro-inflammatory roles, MSCs may be immunomodulatory and have potential therapeutic value to modulate immune responses favorably in these autoimmune conditions. In this review, the complex role and interactions between MSCs and the haematopoietically derived immune cells in RA and SLE are discussed. The harnessing of MSC immunomodulatory effects by contact-dependent and independent mechanisms, including MSC secretome and extracellular vesicles, is discussed in relation to RA and SLE considering the stromal immune microenvironment in the diseased joints. Data from translational studies employing MSC infusion therapy against inflammation in other settings are contextualized relative to the rheumatological setting. Although safety and proof of concept studies exist in RA and SLE supporting experimental and laboratory data, robust phase 3 clinical trial data in therapy-resistant RA and SLE is still lacking.

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Section: Discussionmentioning

confidence: 99%

Multipotent Mesenchymal Stromal Cells in Rheumatoid Arthritis and Systemic Lupus Erythematosus; From a Leading Role in Pathogenesis to Potential Therapeutic Saviors?

et al. 2021

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“…Nonetheless, the field has now departed from a classic view where MSC regenerate mesenchymal tissues in a cell‐for‐cell manner, secretion of growth factors and cytokines stimulating tissue regeneration probably accounting for MSC's main therapeutic benefit . MSC still exhibit the downsides of cells described exclusively in vitro following sustained proliferation: extended culture induces genetic modifications and MSC malignant transformation has been occasionally reported, adding to the inherent ability of these cells to participate in tumor stroma development . Such a genetic instability, added to unpredictable clonal selection, diversity of organ sources, and differences in culture conditions practiced in distinct laboratories, are likely to account for reported discrepancies in the biological and, by extension, therapeutic properties of these cultured cells.…”

Section: Discussionmentioning

confidence: 99%

Perivascular Mesenchymal Progenitors for Bone Regeneration

James

Péault

2019

Journal Orthopaedic Research

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Mesenchymal progenitor cells reside in all assayed vascularized tissues, and are broadly conceptualized to participate in homeostasis/renewal and repair. The application of mesenchymal progenitor cells has been studied for diverse orthopaedic conditions related to skeletal degeneration, regeneration, and tissue fabrication. One common niche for mesenchymal progenitors is the perivascular space, and in both mouse and human tissues, perivascular progenitor cells have been isolated and characterized. Of these “perivascular stem cells” or PSC, pericytes are the most commonly studied cells. Multiple studies have demonstrated the regenerative properties of PSC when applied to bone, including direct osteochondral differentiation, paracrine‐induced osteogenesis and vasculogenesis, and immunomodulatory functions. The confluence of these effects have resulted in efficacious bone regeneration across several preclinical models. Yet, key topics of research in perivascular progenitors highlight our lack of knowledge regarding these cell populations. These ongoing areas of study include cellular diversity within the perivascular niche, tissue‐specific properties of PSC, and factors that influence PSC‐mediated regenerative potential. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1221–1228, 2019.

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“…On the negative side, MSCs are the cultured product of a heterogeneous mixture of unseparated cells, and in vitro growth involves cell exposure to animal proteins, hence chances of xenogeneic immunization, and entails risks of bacterial contamination and genetic instability. There have been occasional reports of MSC malignant transformation [51]; principally, it is increasingly accepted that MSC recruitment to the tumor stroma can favor cancer development [52]. For all these reasons, it might be beneficial to use purified, non-cultured perivascular cells in place of culture-derived MSCs for cell therapies.…”

Section: Discussionmentioning

confidence: 99%

Pericytes for Therapeutic Bone Repair

Meyers

Casamitjana

Chang

et al. 2018

Advances in Experimental Medicine and Biology

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Besides seminal functions in angiogenesis and blood pressure regulation, microvascular pericytes possess a latent tissue regenerative potential that can be revealed in culture following transition into mesenchymal stem cells. Endowed with robust osteogenic potential, pericytes and other related perivascular cells extracted from adipose tissue represent a potent and abundant cell source for refined bone tissue engineering and improved cell therapies of fractures and other bone defects. The use of diverse bone formation assays in vivo, which include mouse muscle pocket osteogenesis and calvaria replenishment, rat and dog spine fusion, and rat non-union fracture healing, has confirmed the superiority of purified perivascular cells for skeletal (re)generation. As a surprising observation though, despite strong endogenous bone-forming potential, perivascular cells drive bone regeneration essentially indirectly, via recruitment by secreted factors of local osteo-progenitors.

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Tumor Formation of Adult Stem Cell Transplants in Rodent Arthritic Joints

Cited by 14 publications

References 60 publications

Multipotent Mesenchymal Stromal Cells in Rheumatoid Arthritis and Systemic Lupus Erythematosus; From a Leading Role in Pathogenesis to Potential Therapeutic Saviors?

Multipotent Mesenchymal Stromal Cells in Rheumatoid Arthritis and Systemic Lupus Erythematosus; From a Leading Role in Pathogenesis to Potential Therapeutic Saviors?

Perivascular Mesenchymal Progenitors for Bone Regeneration

Pericytes for Therapeutic Bone Repair

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