Bone Marrow–Derived and Adipose‐Derived Mesenchymal Stem Cell Therapy in Primary Knee Osteoarthritis: A Narrative Review

Jayaram, Prathap; Ikpeama, Uzoh E.; Rothenberg, Joshua; Malanga, Gerard A.

doi:10.1016/j.pmrj.2018.06.019

Cited by 48 publications

(37 citation statements)

References 50 publications

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“…Human adipose-derived stem cells (ADSCs) are a common type of mesenchymal stem cell (MSC) and have been mainly used in regenerative medicine for treating various diseases [1][2][3][4][5][6] including osteoarthritis, degenerative arthritis, cartilage or tendon injury, graft-versus-host diseases, chronic kidney diseases, etc. Currently, ADSCs are among the mostly used stem cell sources in the cell transplantation field [7][8][9][10][11] . As of 17 September 2019, there were 994 MSC clinical trials registered at clinicaltrials.org (either completed or recruiting), of which 176 (17.7% of all MSC trials) were using human adipose-derived MSCs.…”

Section: Introductionmentioning

confidence: 99%

Neurospheres Induced from Human Adipose-Derived Stem Cells as a New Source of Neural Progenitor Cells

Peng

et al. 2019

Cell Transplant

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Human adipose-derived stem cells are used in regenerative medicine for treating various diseases including osteoarthritis, degenerative arthritis, cartilage or tendon injury, etc. However, their use in neurological disorders is limited, probably due to the lack of a quick and efficient induction method of transforming these cells into neural stem or progenitor cells. In this study, we reported a highly efficient and simple method to induce adipose-derived stem cells into neural progenitor cells within 12 hours, using serum-free culture combined with a well-defined induction medium (epidermal growth factor 20 ng/ml and basic fibroblast growth factor, both at 20 ng/ml, with N2 and B27 supplements). These adipose-derived stem cell-derived neural progenitor cells grow as neurospheres, can self-renew to form secondary neurospheres, and can be induced to become neurons and glial cells. Real-time polymerase chain reaction showed significantly upregulated expression of neurogenic genes Sox2 and Nestin with a moderate increase in stemness gene expression. Raybio human growth factor analysis showed a significantly upregulated expression of multiple neurogenic and angiogenic cytokines such as brain-derived neurotrophic factor, glial cell line-derived neurotrophic growth factor, nerve growth factor, basic fibroblast growth factor and vascular endothelial growth factor etc. Therefore, adipose-derived stem cell-derived neurospheres can be a new source of neural progenitor cells and hold great potential for future cell replacement therapy for treatment of various refractory neurological diseases.

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Section: Introductionmentioning

confidence: 99%

Neurospheres Induced from Human Adipose-Derived Stem Cells as a New Source of Neural Progenitor Cells

Peng

et al. 2019

Cell Transplant

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“…There are mixed reports on the effect of intra-articular MSCs on OA structural pathology, potentially related to differences in cell source (e.g. autologous versus heterologous, marrow-versus adipose-derived, directly isolated stromal cells versus culture-expanded), cell number, carrier, timing of administration, outcome measures evaluated, and animal model used, amongst others [21,41,42]. Our data showing chondroprotective effects of heterologous marrow-derived culture-expanded MSCs contrasts with a recent study using adipose-derived MSCs in the same DMM model [23].…”

Section: Discussionmentioning

confidence: 99%

The relationship between synovial inflammation, structural pathology, and pain in post-traumatic osteoarthritis: differential effect of stem cell and hyaluronan treatment

et al. 2020

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Background: Synovitis is implicated in the severity and progression of pain and structural pathology of osteoarthritis (OA). Increases in inflammatory or immune cell subpopulations including macrophages and lymphocytes have been reported in OA synovium, but how the particular subpopulations influence symptomatic or structural OA disease progression is unclear. Two therapies, hyaluronan (HA) and mesenchymal stem cells (MSCs), have demonstrated efficacy in some clinical settings: HA acting as device to improve joint function and provide pain relief, while MSCs may have immunomodulatory and disease-modifying effects. We used these agents to investigate whether changes in pain sensitization or structural damage were linked to modulation of the synovial inflammatory response in post-traumatic OA. Methods: Skeletally mature C57BL6 male mice underwent medial-meniscal destabilisation (DMM) surgery followed by intra-articular injection of saline, a hyaluronan hexadecylamide derivative (Hymovis), bone marrow-derived stem cells (MSCs), or MSC + Hymovis. We quantified the progression of OA-related cartilage, subchondral bone and synovial histopathology, and associated pain sensitization (tactile allodynia). Synovial lymphocytes, monocyte/ macrophages and their subpopulations were quantified by fluorescent-activated cell sorting (FACS), and the expression of key inflammatory mediators and catabolic enzyme genes quantified by real-time polymerase chain reaction (PCR). Results: MSC but not Hymovis significantly reduced late-stage (12-week post-DMM) cartilage proteoglycan loss and structural damage. Allodynia was initially reduced by both treatments but significantly better at 8 and 12 weeks by Hymovis. Chondroprotection by MSCs was not associated with specific changes in synovial inflammatory cell populations but rather regulation of post-injury synovial Adamts4, Adamts5, Mmp3, and Mmp9 expression. Reduced acute post-injury allodynia with all treatments coincided with decreased synovial macrophage and T cell numbers, while longer-term effect on pain sensitization with Hymovis was associated with increased M2c macrophages. Conclusions: This therapeutic study in mice demonstrated a poor correlation between cartilage, bone or synovium (histo)pathology, and pain sensitization. Changes in the specific synovial inflammatory cell subpopulations may be associated with chronic OA pain sensitization, and a novel target for symptomatic treatment.

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“…MSCs derived from bone marrow do not differ from those derived from adipose tissue as they share their pericyte origin, surface markers, gene expression and potential for differentiation. Another important consideration is the amount of MSCs that can be derived from different harvesting sites: a gram of adipose tissue provides about 300 times more MSCs than a mL of bone marrow aspirate [ 216 ]. Considering the difference in harvested volume, AMFAT appears to be a more favorable method [ 217 ].…”

Section: State-of-the-art Non-operative Therapeutic Considerationmentioning

confidence: 99%

Knee Osteoarthritis: A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations

Primorac

Molnar

Rod

et al. 2020

Genes

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Being the most common musculoskeletal progressive condition, osteoarthritis is an interesting target for research. It is estimated that the prevalence of knee osteoarthritis (OA) among adults 60 years of age or older is approximately 10% in men and 13% in women, making knee OA one of the leading causes of disability in elderly population. Today, we know that osteoarthritis is not a disease characterized by loss of cartilage due to mechanical loading only, but a condition that affects all of the tissues in the joint, causing detectable changes in tissue architecture, its metabolism and function. All of these changes are mediated by a complex and not yet fully researched interplay of proinflammatory and anti-inflammatory cytokines, chemokines, growth factors and adipokines, all of which can be measured in the serum, synovium and histological samples, potentially serving as biomarkers of disease stage and progression. Another key aspect of disease progression is the epigenome that regulates all the genetic expression through DNA methylation, histone modifications, and mRNA interference. A lot of work has been put into developing non-surgical treatment options to slow down the natural course of osteoarthritis to postpone, or maybe even replace extensive surgeries such as total knee arthroplasty. At the moment, biological treatments such as platelet-rich plasma, bone marrow mesenchymal stem cells and autologous microfragmented adipose tissue containing stromal vascular fraction are ordinarily used. Furthermore, the latter two mentioned cell-based treatment options seem to be the only methods so far that increase the quality of cartilage in osteoarthritis patients. Yet, in the future, gene therapy could potentially become an option for orthopedic patients. In the following review, we summarized all of the latest and most important research in basic sciences, pathogenesis, and non-operative treatment.

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Bone Marrow–Derived and Adipose‐Derived Mesenchymal Stem Cell Therapy in Primary Knee Osteoarthritis: A Narrative Review

Cited by 48 publications

References 50 publications

Neurospheres Induced from Human Adipose-Derived Stem Cells as a New Source of Neural Progenitor Cells

Neurospheres Induced from Human Adipose-Derived Stem Cells as a New Source of Neural Progenitor Cells

The relationship between synovial inflammation, structural pathology, and pain in post-traumatic osteoarthritis: differential effect of stem cell and hyaluronan treatment

Knee Osteoarthritis: A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations

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