Intra-articular interventions in osteoarthritis: Navigating the landscape of hyaluronic acid, mesenchymal stem cells, and platelet-rich plasma

Table 1 Summary of different treatment modalities

MSCs	PRP	HA
(1) SC therapy utilizes various types of stem cells, such as those derived from adipose tissue, bone marrow, and the umbilical cord	(1) PRP contains elevated platelet concentrations and is used for tissue healing and regeneration, especially in conditions like OA	(1) Various HA derivatives are used for knee OA management, such as Hylan polymers, sodium hyaluronate and hyaluronan
(2) AD-MSC intra-articular injections showed significant clinical and structural knee joint improvement over 6 and 12 mo, respectively	(2) In a laboratory study, PRP and high molecular weight HA were compared in their effects on gene expression and secretion of inflammatory mediators from OA cartilage and synoviocytes	(2) Hylan G-F20, a cross-linked HA product, has demonstrated effectiveness in relieving pain and improving function in knee OA, as well as delaying the need for total knee replacement
(3) UC-MSC intra-articular injections showed significant clinical improvement over 12 mo with multiple injections, however, no structural improvement was observed	(3) PRP injections were found effective even in late-stage knee OA, enhancing pain relief and daily life activities	(3) Sodium hyaluronate, such as Supartz, has demonstrated significant pain reduction and improved function in mild to moderate symptomatic knee OA
(4) BM-MSC intra-articular injections did not show significant clinical or structural improvement	(4) Optimal dosage of PRP with 10 billion platelets showed significant improvements in WOMAC and IKDC scores, along with decreased inflammatory markers like IL-6 and TNF-α	(4) The clinical benefits of hyaluronan injections compared to placebo remain inconclusive, suggesting the need for head-to-head comparisons with other HA preparations
(5) Intra-articular injection of MSCs for OA is a safe treatment that showed no major adverse events	(5) PRP intra-articular injection has promising results for moderate to severe OA symptoms enhancement, regardless of leukocyte richness	(5) Current guidelines regarding viscosupplementation for knee OA are inconclusive and may evolve with emerging data supporting HA injections
	(6) Intraosseous injections of PRP did not provide additional benefits in OA knee treatment compared to intra-articular injections alone	(6) Safety assessments indicate slightly higher local adverse effects with intra-articular HA injections compared to placebo, but fewer systemic side effects than oral NSAIDs or acetaminophen
		(7) Viscosupplementation may offer symptom relief but does not reverse the arthritic process or promote cartilage regeneration, emphasizing the need for ongoing research into its efficacy and long-term effects

PRP: Platelet-rich plasma; OA: Osteoarthritis; MSCs: Mesenchymal stem cells; HA: Hyaluronic acid; UC-MSC: Umbilical cord derived mesenchymal stem cells; BM-MSC: Bone marrow-derived mesenchymal stem cells; WOMAC: Western Ontario and McMaster Universities Osteoarthritis index; IKDC: International Knee Documentation Committee; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-α; NSAIDs: Nonsteroidal anti-inflammatory drugs.

Table 2 Comparison between different treatment modalities

MSCs to PRP	PRP to HA	HA to MSCs
(1) Both MSCs and PRP intra-articular injections resulted in pain relief and overall clinical improvement over similar time frames	(1) Both PRP and HA alleviated catabolism, but PRP showed better reduction in cartilage breaking enzymes and increased cartilage synthetic activity	(1) AD-MSC therapy demonstrated superior efficacy over HA injections
(2) Both MSCs and PRP showed significantly better clinical improvement when compared to HA	(2) In a randomized clinical trial, PRP demonstrated superiority over HA in long-term pain reduction and improvement in quality of life for OA patients	(2) AD-MSC-treated patients showed increased knee cartilage volume at 12 mo, indicating potential long-term structural benefits compared to HA
(3) Unlike PRP, AD-MSCs resulted in significant structural improvement, suggesting that they could serve as a more effective long-term treatment option for knee OA	(3) Comparisons between leukocyte-poor PRP and HA showed significant improvement with PRP in WOMAC and IKDC scores at 12 mo	(3) UC-MSC injections, administered in multiple doses, led to superior long-term clinical improvements in knee OA, in comparison to HA injections
		(4) Neither UC-MSC nor HA injections showed structural improvement on radiological outcomes, suggesting potential limitations of both therapies in addressing OA progression
		(5) HA injections offer temporary relief lasting up to several months, compared to UC-MSCs that can last up to 33 mo with invasive methods
		(6) Injections and MSC therapy exhibit favorable safety profiles, with few severe adverse events reported

PRP: Platelet-rich plasma; OA: Osteoarthritis; MSCs: Mesenchymal stem cells; HA: Hyaluronic acid; UC-MSC: Umbilical cord derived mesenchymal stem cells; WOMAC: Western Ontario and McMaster Universities Osteoarthritis index; IKDC: International Knee Documentation Committee.