Research Articles

Supporting Stem Cell Therapy

Research articles supporting stem cell therapy related to procedures

https://ard.bmj.com/content/79/Suppl_1/1738.3

CONSENSUS STATEMENT ON INTRA-ARTICULAR INJECTIONS OF PLATELET-RICH PLASMA FOR THE MANAGEMENT OF KNEE OSTEOARTHRITIS

Results: The main recommendations are listed below:

– Intra-articular injections of PRP constitute an efficient treatment of early or moderate symptomatic knee osteoarthritis.

– Intra-articular injections of PRP may be useful in severe knee osteoarthritis

– Intra-articular injections of PRP in knee osteoarthritis should be proposed as second-line therapy, after failure of non-pharmacological and pharmacological (oral and topic) symptomatic treatment.

– Intra-articular injections of PRP should not be performed in osteoarthritis flare-up with significant effusion.

– Intra-articular PRP treatment may include 1 to 3 consecutive injections.

– Leukocyte-poor PRP should be preferred for knee OA treatment.

– PRP injections should be performed under ultrasound or fluoroscopic guidance.

– PRP should not be mixed with injectable anesthetic or corticosteroid.

Conclusion: Twenty-five recommendations were discussed by an international multidisciplinary task force group in order to provide a basis for standardization of clinical practices and future research protocols.


https://pubmed.ncbi.nlm.nih.gov/29790618/

Intratendinous Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Rotator Cuff Disease: A First-In-Human Trial

Intratendinous injection of AD MSCs was not associated with adverse events. It significantly decreased the SPADI scores by 80% and 77% in the mid- and high-dose groups, respectively. Shoulder pain was significantly alleviated by 71% in the high-dose group. Magnetic resonance imaging examination showed that volume of the bursal-side defect significantly decreased by 90% in the high-dose group. Arthroscopic examination demonstrated that volume of the articular- and bursal-side defects decreased by 83% and 90% in the mid- and high-dose groups, respectively. Intratendinous injection of autologous AD MSCs in patient with a partial-thickness rotator cuff tear did not cause adverse events, but improved shoulder function, and relieved pain through regeneration of rotator cuff tendon. Stem Cells 2018;36:1441-1450.


https://www.painmedicinenews.com/Interventional/Article/11-20/International-Task-Force-Issues-Recommendations-For-Intraarticular-PRP-Injections-for-Knee-OA/61101?sub=84B0DB3BDA18194B2DF70C045CF7912F658F7FB4F34DEE2749C7B9A7CD821A&enl=true&dgid=X3624150&utm_source=enl&utm_content=1&utm_campaign=20201123&utm_medium=button

A team of 15 physicians (10 rheumatologists, four specialists in rehabilitation and sports medicine, and an interventional radiologist) from different countries provided their expertise for the recommendations. All experts voted their agreement or disagreement with each recommendation using a score between 1 (totally inappropriate) and 9 (totally appropriate). Depending on the median value and extreme scores, recommendations were judged as appropriate, inappropriate or uncertain due to indecision or absence of consensus. This process resulted in these main recommendations:

  • Intraarticular injections of PRP constitute an efficient treatment for early or moderate symptomatic knee osteoarthritis (median score, 8; appropriate).
  • Intraarticular injections of PRP may be useful in severe knee osteoarthritis (median score, 7; appropriate).
  • Intraarticular injections of PRP in knee osteoarthritis should be proposed as a second-line therapy after failure of nonpharmacologic and pharmacologic (oral and topical) symptomatic treatment (median score, 9; appropriate).
  • Intraarticular injections of PRP should not be performed in osteoarthritis flare-up with significant effusion (median score, 7; appropriate).
  • Intraarticular PRP treatment may include one to three consecutive injections (median score, 9; appropriate).
  • Leukocyte-poor PRP should be preferred for knee OA treatment (median score, 8; appropriate).
  • PRP injections should be performed under ultrasound or fluoroscopic guidance (median score, 8; uncertain).
  • PRP should not be mixed with injectable anesthetic or corticosteroid (median score, 9; appropriate).

https://pubmed.ncbi.nlm.nih.gov/32536765/

Effectiveness of Adipose-MSCs injections for the treatment of knee osteoarthritis: Analysis of the current literature

Conclusion: Our data suggest that the intra-articular injection of autologous AD-MSCs is a safe and effective therapeutic alternative for the treatment of severe knee OA patients and may have the potential to attenuate progression of the disease.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083980/

Stem Cell Treatment for Knee Articular Cartilage Defects and Osteoarthritis

Abundant literature describing the preclinical efficacy of MSCs in treating degenerative conditions of the knee has emerged in the last several years.  MSCs are a broad category of adult multipotent stromal cells that have the potential to self-renew and directionally differentiate into multiple lineages of cells including osteoblasts (bone), adipocytes (fat and marrow), myocytes (muscle), and chondrocytes (cartilage) [9, 10].  

The authors also noted statistically significant improvement in mean cartilage thickness measured on T2-weighted MRI; no adverse events were described.

https://pubmed.ncbi.nlm.nih.gov/31456015/

Improved outcomes after mesenchymal stem cells injections for knee osteoarthritis: results at 12-months follow-up: a systematic review of the literature

Results: A total of 18 studies were enrolled in the present study, comprising 1069 treated knees. The mean age of the samples was 57.39 ± 7.37 years. 72% of the included studies harvested the stem cells from the iliac crest (bone marrow-derived MSCs), the remaining 28% from the adipose tissue (adipose-derived MSCs). The mean visual analogic scale improved from 18.37 to 30.98 and 36.91 at 6- and 12-month follow-up, respectively. The mean WOMAC score improved from 25.66 to 25.23 and 15.60 at 6- and 12-month follow-up, respectively. The mean walking distance improved from 71.90 to 152.22 and 316.72 at 6- and 12-month follow-up, respectively. The mean Lequesne scale improved from 33.76 to 12.90 at 12-month follow-up. The KOOS score improved from 41.07 to 8.47% and 18.94 at 6- and 12-month follow-up. All the KOOS subscales improved significantly from the baseline. A total of 136 (12.7%) local complications were detected.

Conclusion: According to the current evidences and the main findings of this systematic review, we reported that MSC infiltrations for knee OA can represent a feasible option, leading to an overall remarkable improvement of all clinical and functional considered outcomes, regardless of the cell source. Patients treated at earlier-degeneration stages reported statistically significant greater outcomes. The pain and function scores were improved considerably, thus, leading to a significant improvement of patient participation in recreational activities and quality of life.


https://pubmed.ncbi.nlm.nih.gov/32111220/

Injections of concentrated bone marrow aspirate as treatment for Discogenic pain: a retrospective analysis

Results: At least 50% improvement in NRS was observed for 13.8, 45.8, 41.1, 23.5, and 38.9% of patients across five follow-up visits, out to 1 year. When stratified by high (> 5) versus low (≤ 5) baseline NRS scores, the values were 14.3, 45.5, 71.4, 22.2, and 44.4% among those with high baseline pain, and 13.3, 46.2, 20.0, 25.0, and 33.3% among those with low baseline pain. The 50% improvement rates across visits were 4.3, 28.6, 30.0, 22.2, and 30.8% for SF-36, and 4.2, 26.7, 36.4, 55.6, and 30.8% for ODI.

Conclusions: Intradiscal cBMA injections may be effective to reduce pain and improve function. Patients with relatively higher initial pain may have potential for greatest improvement.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384917/

Current perspectives in stem cell therapies for osteoarthritis of the knee

Recently, mesenchymal stem cells (MSCs) have been in the spotlight for their disease-modifying and chondrogenic potential along with their ease of harvesting, safety, and differentiation potential into cartilage.

Umbilical cord compartments including Wharton’s jelly, perivascular tissue, and umbilical cord blood (UCB) can be utilized to isolate MSCs [43,63]. Umbilical cord-derived MSCs can be obtained through pain-free collection methods with fewer ethical issues. An experimental comparative study [64] confirmed that UCB-MSCs have biological advantages in comparison to bone marrow or adipose tissue, including higher rate of proliferation and clonality, retardation of senescence, and superior anti-inflammatory effect.  hUCB-MSCs are also isolated in a non-invasive manner and have the advantage of being hypoimmunogenic. Moreover, they show a hyaline-like histological morphology [67]. Park et al. [65] reported that an hUCB-MSC-based product appeared safe and effective for the regeneration of hyaline-like cartilage in OA of the knee after 7 years of follow-up. In our institution, commercialized hUCB-MSCs were performed on OA of the knee to obtain favorable clinical outcomes and highly qualified regeneration. Adipose tissue, along with bone marrow, has been the most frequently used source for isolating MSCs [43]. Adipose tissue is abundant and easily accessible, making it a reliable site for stem cell isolation. It has copious numbers of MSCs (approximately 0.5×104–2.0×105/1 g fat) compared to BM-MSCs and their differential capacity is relatively less affected by donor age.  Several studies have reported encouraging clinical results for intra-articular injection of AD-MSCs in knee OA patients (Table 2) [14,50-53]. Lee et al. [50] reported that intra-articular injection of culture expanded AD-MSCs (1×108 cells) showed satisfactory functional improvement and pain relief in patients with knee OA through a prospective randomized controlled trial.


https://pubmed.ncbi.nlm.nih.gov/32840122/

Does the Source of Mesenchymal Stem Cell Have an Effect in the Management of Osteoarthritis of the Knee? Meta-Analysis of Randomized Controlled Trials

Results: Nineteen studies involving 811 patients were included for analysis.  At 6 months, AD-MSCs showed significantly better VAS(P<0.001,P=0.069) and WOMAC(P=0.134,P=0.441) improvement than BM-MSCs, respectively, compared to controls. At 1 year, AD-MSCs outperformed BM-MSCs compared to their control in measures like WOMAC(P=0.007,P=0.150), KOOS(P<0.001;P=0.658), and WORMS(P<0.001,P=0.041), respectively. Similarly at 24 months, AD-MSCs showed significantly better Lysholm score(P=0.037) than BM-MSCs(P=0.807) although VAS improvement was better with BM-MSCs at 24 months(P<0.001). There were no significant adverse events with either of the MSCs compared to their controls.

Conclusion: Our analysis establishes the efficacy, safety, and superiority of AD-MSC transplantation, compared to BM-MSC, in the management of osteoarthritis of knee from available literature.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178263/

Stem cell application for osteoarthritis in the knee joint: A minireview

Total knee replacements come together with high effort and costs and are not always successful.  The aim of this review is to outline the latest advances in stem cell therapy for knee osteoarthritis as well as highlight some of the advantages of stem cell therapy over traditional approaches aimed at restoration of cartilage function in the knee.

In general, MSC related therapeutic approaches have a significant advantage to traditional surgical approaches such as autologous chondrocyte transplantation: no cartilage biopsy is necessary, thus no external stress and cellular damage are applied at the donor-site articular surface[31]. Moreover, direct intra-articular injection of MSC is perceived as a technically simple way to treat advanced OA of the knee.


https://pubmed.ncbi.nlm.nih.gov/30545387/

A specific protocol of autologous bone marrow concentrate and platelet products versus exercise therapy for symptomatic knee osteoarthritis: a randomized controlled trial with 2 year follow-up.

Conclusion: After BMC treatment, patients’ clinical outcome scores (except SF-12 Mental Health), were significantly improved through the 2-year follow-up compared to baseline. No serious adverse events were reported.  The use of image-guided percutaneous BMC with platelet products yielded better results than exercise therapy as an effective alternative therapy for patients with symptomatic moderate to moderate-severe osteoarthritis of the knee. Trial registration NCT02034032. https://clinicaltrials.gov/ct2/show/NCT02034032 . Registered 13 January 2014. 


https://pubmed.ncbi.nlm.nih.gov/29790618/

Intratendinous Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Rotator Cuff Disease: A First-In-Human Trial

Intratendinous injection of AD MSCs was not associated with adverse events. It significantly decreased the SPADI scores by 80% and 77% in the mid- and high-dose groups, respectively. Shoulder pain was significantly alleviated by 71% in the high-dose group. Magnetic resonance imaging examination showed that volume of the bursal-side defect significantly decreased by 90% in the high-dose group. Arthroscopic examination demonstrated that volume of the articular- and bursal-side defects decreased by 83% and 90% in the mid- and high-dose groups, respectively. Intratendinous injection of autologous AD MSCs in patient with a partial-thickness rotator cuff tear did not cause adverse events, but improved shoulder function, and relieved pain through regeneration of rotator cuff tendon. Stem Cells 2018;36:1441-1450.


https://pubmed.ncbi.nlm.nih.gov/32252731/

The influence of adipose-derived stromal vascular fraction cells on the treatment of knee osteoarthritis

Fifty-seven patients were enrolled and treated with intra-articular injection of 2.5 × 107 SVF cells into the knee joint between September 2017 and March 2018. All patients were followed up for 12 months or longer. Mean age at treatment and follow-up period were 69.4 ± 6.9 years and 13.7 ± 2.0 months, respectivelyResults: Knee extension angle at 6 and 12 months postoperatively was significantly better than the preoperative angle. Total WOMAC, VAS, and KOOS scores at 1, 3, 6 and 12 months postoperatively were significantly better than preoperative scores.  Conclusions: The short-term clinical effects of intra-articular SVF cell injection on knee OA were excellent. Intra-articular SVF cell injection is a novel and innovative approach for treating patients with knee OA.


https://pubmed.ncbi.nlm.nih.gov/30715002/

Mesenchymal Stem Cells injection in hip osteoarthritis: preliminary results.

Mesenchymal stem cells (MSC) have the inner ability to mature into different types of cells depending on the stimuli they undergo. This technique has already been proven successful in the knee and, with this retrospective study, we would like to assess its feasibility in the hip joint.  Results: The HHS showed an improvement from the pre-operative baseline mean value of 67.2±3.4 to the 84.6±6.3 post-operative value. Moreover, the WOMAC score dropped from a baseline score of 36.3±4.7 to 19.8±3.4 at 6 months’ post-op follow up visit.

Conclusions: MSC Lipogems is a fairly easy technique. No adverse effects were recorded in our experience.


https://www.ncbi.nlm.nih.gov/pubmed/25953464

Human Adipose Stem Cells: From Bench to Bedside.

Adult stem cells currently symbolize the most available source of cell progenitors for tissue engineering and repair and can be harvested using minimally invasive procedures. Moreover, mesenchymal stem cells (MSCs), the most widely used stem cells in stem cell-based therapies, are multipotent progenitors, with capability to differentiate into cartilage, bone, connective, muscle, and adipose tissue.  So far, bone marrow has been regarded as the main source of MSCs. To date, human adult adipose tissue may be the best suitable alternative source of MSCs.


https://jmsgr.tamhsc.edu/umbilical-cord-derived-mesenchymal-stem-cells-are-best-suited-for-cartilage-and-bone-regeneration/

Conclusions.  Mesenchymal stem cells are a great alternative option for cartilage and bone repair. Wharton jelly-derived mesenchymal stem cells are better suited because of their immunosuppressive activity. Lack of teratomas, painless collection procedure, faster proliferation rates and hypoimmunogenicity make WJ-MSCs safe & effective for cartilage regeneration.  Studies have shown the beneficial use of bone marrow derived mesenchymal stem cells (MSCs), however, emerging research shows that Wharton jelly derived MSCs (WJ-MSCs) are best suited for cartilage regeneration.


https://jmsgr.tamhsc.edu/emerging-technologies-advances-in-tissue-engineering-using-mesenchymal-stem-cells-and-scaffolds-in-rotator-cuff-repair/

The literature offers compelling evidence to suggest that the placement of scaffolds seeded with MSCs into the tendon repair site during surgical repair of RC tears may provide improved overall recovery and a reduction in reinjury for patients.


https://jmsgr.tamhsc.edu/chrondrogenesis-of-mesenchymal-stem-cells-for-the-treatment-of-osteoarthritis/  Conclusion.     Chondrogenesis of MSCs can benefit patients suffering from OA in two manners. The anti-inflammatory effects of MSCs can reduce synovial inflammation and the chondrogenesis can help restore lost mass of cartilage.

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