Current Perspectives in Mesenchymal Stem Cell Therapies for Osteoarthritis

Table 1

Chronological list of publications utilising MSCs for cartilage repair in OA patients.

Study	Study type	Number of patients receiving MSCs	Delivery system	Number of cells	Follow-up time	Control group	MSCs origin	Conclusion
Wakitani et al. 2002 [61]	Case and control study	12	HTO, implantation of cell sheets, gel-cell composite	1.3 × 10^7	28–95 weeks	12 cell-free controls	Autologous BMSCs from Iliac crest	Autologous BMSCs cell implants are effective for treating OA cartilage defects in humans and producing hyaline-like cartilage
Wakitani et al. 2004 [60]	Case studies	2	Surgery, implantation of collagen cell sheets	N/A	48–69 months	None	Autologous BMSCs from Iliac crest	Autologous BMSCs can be implanted into full thickness articular cartilage defects where they produce fibrocartilage
Kuroda et al. 2007 [62]	Case study	1	Medial parapatellar approach, implantation of collagen cell sheets	5.0 × 10^6 cells/mL	12 months	None	Autologous BMSCs from Iliac crest	Autologous BMSCs cell implants can promote the repair of large focal articular cartilage defects in young, active patients
Wakitani et al. 2007 [63]	Case studies	3	Medial parapatellar approach, implantation, collagen cell sheets	5.0 × 10^6 cells/mL	17–27 months	None	Autologous BMSCs from Iliac crest	Autologous BMSCs cell implants can fully cover full thickness articular defects
Centeno et al. 2008 [70]	Case study	1	Intra-articular injection	2.24 × 10^7	3 months	None	Autologous BMSCs from Iliac crest	Autologous BMSCs can be introduced by intra-articular injections into an osteoarthritic knee which promotes cartilage regeneration and reduction of pain
Centeno et al. 2008 [71]	Case study	1	Intra-articular injection	4.56 × 10^7	3 months	None	Autologous BMSCs from posterior superior iliac spine	Autologous BMSCs introduced by intra-articular injections into an osteoarthritic knee increase meniscus volume
Nejadnik et al. 2010 [66]	Cohort study	36	ACI surgery, implantation of cell sheets	1.0 × 10^7–1.5 × 10^7	24 months	36 patients receiving chondrocyte treatment	Autologous BMSCs from Iliac crest	Autologous BMSCs treatment is as effective as autologous chondrocyte implantations in cartilage repair, additionally reducing morbidity and cost
Buda et al. 2010 [67]	Case series	20	Arthroscopic debridement, implantation, hyaluronic acid membrane scaffold	N/A (2 mL of bone marrow concentrate)	24 months	None	Autologous BMSCs from Iliac crest	One-step repair technique utilising bone marrow concentrate is a simple and time-efficient way to treat large chondral defects
Varma et al. 2010 [84]	Randomized control trial	25	Arthroscopic debridement, intra-articular injection	N/A	N/A	25 cell-free controls	N/A	The technique applied in this study improved the overall osteoarthritis outcome score, especially the quality of life
Centeno et al. 2010 [53]	Case series	227	Intra-articular injection	N/A	Up to 24 months	None	Autologous BMSCs from posterior superior iliac spine	Intra-articular injections of autologous BMSCs are a safe method resulting in no ectopic formations or malignant transformations
Wakitani et al. 2011 [64]	Case series	41	Surgery, implantation, cell sheets, gel-cell composite	5.0 × 10^6 cells/mL	5–137 months	None	Autologous BMSCs from Iliac crest	Autologous BMSCs implantations are a safe way to treat articular cartilage defects, resulting in no tumour formation or infections
Saw et al. 2011 [77]	Case studies	5	Microfracture, 5 intra-articular injections	N/A (7-8 mL of PBPCs)	10–26 months	None	Autologous PBPCs	Microfracture and injections of autologous PBPCs in combination with HA can regenerate articular hyaline cartilage
Gobbi et al. 2011 [68]	Case series	15	Miniarthrotomy, implantation of collagen cell sheets	Bone marrow concentrate from 60 mL of bone marrow	24–38 months	None	Autologous BMSCs from Iliac crest	One-step repair technique utilising bone marrow concentrate and collagen I/III is efficient in repairing chondral defects
Davatchi et al. 2011 [72]	Case series study	4	Intra-articular injection	8-9 × 10^6	12 months	None	Autologous BMSCs	Intra-articular injections of BMSCs into OA knees improved the VAS scores; while not excellent, the results were encouraging
Koh and Choi 2012 [79]	Case and control study	25	Arthroscopic debridement, synovectomy, and intra-articular injection	1.2–2.3 × 10^6	12–18 months	25 cell-free controls	Autologous AMSCs from infrapatellar fat pad	Intra-articular injections of AMSCs are a safe treatment option, reducing pain and improving the function of knee OA patients
Emadedin et al. 2012 [73]	Case series study	6	Intra-articular injection	2.0–2.4 × 10^7	12 months	None	Autologous BMSCs from Iliac crest	Intra-articular injections of BMSCs into OA knees resulted in no adverse events and improved walking distance and pain scores for the first 6 months, while decreasing in the following 6 months
Orozco et al. 2013 [74]	Case series study	12	Intra-articular injection	40 × 10^6	12 months	None	Autologous BMSCs from Iliac crest	Intra-articular injections of BMSCs resulted in rapid and progressive improvements, significantly improving quality of life reaching up to 78% improvement
Wong et al. 2013 [78]	Randomized control trial	28	HTO, microfracture, and intra-articular injection	1.46 × 10^7	24 months	28 cell-free controls	Autologous BMSCs from Iliac crest	Postoperative intra-articular injections of autologous BMSCs improves the MOCART outcomes of patients with varus knees undergoing HTO and microfracture
Koh et al. 2013 [80]	Case series study	18	Arthroscopic debridement, synovectomy, and intra-articular injection	0.3 × 10^6 to 2.7 × 10^6	24–26 months	None	Autologous AMSCs from infrapatellar fat pad	Intra-articular injections of AMSCs are a safe treatment option, reducing pain and improving the function of knee OA patients
Koh et al. 2013 [81]	Case series study	30	Arthroscopic lavage, intra-articular injection	4.16 × 10^7stromal vascular fraction cells (9.7% = 4.04 × 10^6 stem cells)	24 months	None	Autologous AMSCs from buttocks	Intra-articular injections of AMSCs into OA knees of elderly patients (≥65) are effective in cartilage healing and pain reduction
Saw et al. 2013 [76]	Randomized control trial	25	Microfracture, 8 intra-articular injections	N/A (7-8 mL of PBPCs)	24 months	25 PBPCs free controls	Autologous PBPCs	Microfracture and injections of autologous PBPCs in combination with HA can regenerate articular hyaline cartilage better than microfracture and injection of HA alone
Hauser and Orlofsky 2013 [85]	Case series	6	2–7 intra-articular injections, dextrose prolotherapy	N/A	2–12 months	None	Autologous whole tibial/iliac bone marrow	Intra-articular injections of autologous whole bone marrow are associated with substantial gains in pain relief and functionality
Vangsness et al. 2014 [83]	Randomized, double-blind, controlled study	36	Partial medial meniscectomy, intra-articular injection	5.0 × 10^7, 1.5 × 10^8	24 months	20 cell-free controls	Allogenic BMSCs from 18–30-year-old donors	Postoperative intra-articular injections of allogenic BMSCs contribute to meniscus regeneration and reduction in pain following medial meniscectomy
Jo et al. 2014 [82]	Cohort study	18	Intra-articular injection	1.0 × 10^7, 5.0 × 10^7, 1.0 × 10^8	6 months	None	Autologous AMCSs from abdominal subcutaneous fats	Cartilage regeneration and pain reduction are significantly improved when high amounts of AMSCs are injected into OA knees compared with low amounts
Gobbi et al. 2014 [69]	Case series	25	Miniarthrotomy, implantation of collagen cell sheets	Bone marrow concentrate from 60 mL of marrow	Minimum 36 months	None	Autologous BMSCs from Iliac crest	Large chondral defects can be treated with one-step repair technique