Ultrasound-Guided Intraarticular Injection of Umbilical Cord MSCs for Knee Osteoarthritis

Knee osteoarthritis (KOA) is a common condition affecting the adult population and resulting in a negative impact on quality of life. It is more prevalent in individuals older than 65 years. An estimated 9–14 million adults in the USA alone suffer from KOA. However, the prevalence is increasing among patients younger than 65 years.

As for the pathogenesis of KOA, it can be considered a dynamic disease, with an imbalance between factors that destroy the joint and factors that restore the joint. Several environmental and inflammatory factors play a major role in KOA and may be responsible for its increased prevalence in recent years. Among these are obesity, changes in diet, sedentary lifestyle, and metabolic syndrome.

Current therapies consist of medications to improve symptoms only, mainly pain management with NSAIDs and opioid analgesics being widely prescribed. All pharmacological agents have significant limitations and do not influence the disease course, nor do they offer proper cartilage regeneration.

A Disease-Modifying Therapy

Mesenchymal stem cells (MSCs) have well-recognized potential in cartilage regeneration and can be isolated from many sources, including adipose tissue, bone marrow, umbilical cord (Wharton jelly), placenta, and amniotic fluid. 

Recently, a group of researchers performed a clinical trial evaluating the safety of intraarticular injection of expanded allogeneic umbilical cord (WJMSCs) in patients with knee OA.

Clinical Trial using WJMSCs

The patients were enrolled in a phase 1 study and included a total of 16 patients (25 knees) with moderate or severe non-focal defect KOA.  The patients were followed up for a total of 48 months for any adverse events and for efficacy using a normalized Knee Injury and Osteoarthritis Outcome Score (KOOS). Results of MRI were evaluated at baseline, 6 and 12 months. 

Patients were asked to stop all pain medications and refer to the primary investigator for pain control medications if needed. 

All patients received 2 suprapatellar injections using ultrasound guidance by a senior interventional radiologist, with 1 month of separation. 

MRI Changes

The cartilage damage in baseline images scored mild in 41.7%, moderate in 29.2%, and severe in 20.8%. On follow-up images, it showed an interval decrease in severity at 1 year as follows: mild in 73.3%, moderate in 7.7%, and none with severe cartilage loss. 

The osteophyte formation in baseline images scored mild in 45.8%, moderate in 29.2%, and severe in 20.8%. On follow-up images, it showed an interval decrease in severity at 1 year as follows: mild in 66.7%, moderate in 6.7% and severe in 13.3%.

Joint effusion severity in baseline images scored none in 20.8%, mild in 70.8%, moderate in 4.2%, and severe in 4.2%. On follow-up images, it showed an interval decrease in severity at 1 year as follows: none in 73.3%, mild in 15.4 % and none with moderate or severe effusion.


Of the 16 patients (25 knees treated) who received WJMSCs, none had a serious adverse event for up to 4 years, which shows that the use of these cells via intraarticular injection is safe in KOA. 

A significant improvement was observed in KOOS at 6 months and more improvement at 12 and 48 months. All were statistically highly significant and were maintained even after 4 years of follow-up, indicating a functional disease-modifying therapy. 

Regarding MRI improvement, this was clearly noticed at 12 months with statistically significant improvement in all parameters measured (p < 0.01). The severity of abnormal changes either disappeared or shifted to a milder form and maybe in the long term will disappear.


Samara O, Jafar H, Hamdan M, Al-Ta’mari A, Rahmeh R, Hourani B, Mandalawi N, Awidi A. Ultrasound-guided intra-articular injection of expanded umbilical cord mesenchymal stem cells in knee osteoarthritis: a safety/efficacy study with MRI data. Regen Med. 2022 May 12. doi: 10.2217/rme-2021-0121. Epub ahead of print. PMID: 35546314.

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