Marc Darrow, MD, JD
Marc Darrow MD,JD

In this article I will present research on the use of stem cell therapy treatments for knee osteoarthritis. I will discuss published research by the Darrow Stem Cell Institute on the use of bone marrow derived stem cells. I also invite you to ask your questions using the form below about your knee pain.

“Bone-on-Bone” Arthritis

Many of my patients present with a diagnosis of “bone-on-bone arthritis,” terminology used to describe a knee that has lost all cartilage to cushion the bones. Few actually have true “bone on bone.” If the joint moves, there is typically cartilage present since cartilage is the slippery surface on the end of the bones that allow range of motion.

When the doctor says you have bone-on-bone arthritis, it may be used as an umbrella term to describe various levels of knee degeneration. In the knee joint, cartilage covers the tibia, femur, and the back of the kneecap (the patella); in addition to cartilage, there is the meniscus, which is the fibrous padding between the bones. A healthy knee glides efficiently and painlessly on these structures.

Bone-on-bone can mean that some or all of the cartilage and/or the meniscus have worn down or have defects, thereby causing the bones to rub together. Another diagnostic term that may refer to bone-on-bone is “osteochondral defect.” The term “osteochondral” refers to the cartilage and bone as a unit. Patients often assume that bone-on-bone or an osteochondral defect means extreme and advanced cartilage deterioration, which is not usually the case.

Joint space, the space between the bones, is a challenge to surgeons. If there is no space between the bones, i.e, the cartilage has worn down—surgery cannot restore it. The philosophy then is to manage the knee pain as long as possible (often with repeated steroid injections that temporarily reduce pain, but eventually destroy whatever cartilage is left) prior to the knee replacement surgery.

People are looking for knee replacement options.

The popularity of stem cell therapy over the years has increased for many reasons. Perhaps the most important is that people are looking for knee replacement options. Is stem cell therapy the only option? Far from it. For some people, stem cell therapy may not even be a realistic option.

A November 2021 study (1) goes down the list of available treatments for knee osteoarthritis:

Non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, intra-articular corticosteroid injections are of little value in the long term, and opioids may have ominous consequences. Radiotherapy of knee osteoarthritis has no added value. Physical therapy, exercises, weight loss, and lifestyle modifications may give pain relief, improve physical functioning and quality of life. However, no single treatment has regenerating potential for damaged articular cartilage.

Due to a better understanding of osteoarthritis, innovative new treatment options have been developed . . . (including) intra-articular human serum albumin, conventional disease-modifying anti-rheumatic drugs (DMARDs), lipid-lowering agents (statin), nerve growth factors antagonists, bone morphogenetic protein, fibroblast growth factors, Platelet-Rich Plasma (PRP), Mesenchymal Stem Cells (MSC), exosomes, interleukin-1 blockers, gene-based therapy, and bisphosphonate.”

In our office we focus on Bone Marrow derived Mesenchymal Stem Cells (MSC) and Platelet-Rich Plasma injections.

Stem Cell Therapy Instead of Knee Replacement?

As alluded to in the above paper, over the years it became clear to many researchers that knee replacement had to be redefined and disputed as the gold standard of knee osteoarthritis, “bone-on-bone,” treatment. Other doctors, however, had already decided to abandon joint replacement and explore growing tissue as the new standard of care. The thinking was simple—why remove bone and tissue when these could be repaired and rejuvenated?

What was found in the initial research was intriguing enough to spur on more research. Doctors discovered that one type of stem cell (mesenchymal stem cells found in bone marrow) could morph into bone cells and cartilage cells when injected into a joint. The ramifications for the treatment of osteoarthritis or “bone-on-bone” joints were enormous. Stem cell injections showed that cartilage could be regrown, something that doctors had previously thought impossible because of the cartilage’s limited blood supply within the joint. Most recently, doctors announced that they had confirmed successful regeneration of cartilage tissue in the knee through simple Stem Cell Therapy injection.(2,3)

Before we get to new updates, let’s review the research we conducted at the Darrow Stem Cell Institute in Los Angeles, California on patients with knee osteoarthritis.

Short-Term Outcomes in Treatment of Knee Osteoarthritis With 4 Bone Marrow Concentrate Injections

Brent Shaw, Marc Darrow, MD JD : Darrow Stem Cell Institute, Los Angeles, CA, USA
Armen Derian : Mayo Clinic, Phoenix, AZ, USA
Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders June 18, 2018 (4)
Study synopsis
Preliminary research suggests that bone marrow concentrate (BMC), which contains mesenchymal stem cells and platelets, is a promising treatment for knee osteoarthritis. The aim of this study was to build on this preliminary research by reporting the short-term progress of 15 patients (20 knees) with knee osteoarthritis through 4 BMC (bone marrow derived stem cell treatments.)

The timetable of the four treatments:

  • First treatment
  • Second treatment approximately 14 days after first treatment.
  • Third treatment, approximately 21 days after second treatment, 35 days after first treatment
  • Fourth treatment, approximately 34 days after the third treatment. Approximately 69 days on average after first treatment
  • The last follow-up was conducted a mean 86 days after the first treatment.

What we measured: Overall improvement percentage was compared after each treatment for the following:

  • pain at rest
  • pain during activity
  • functionality scale scores

What we found:

  • Patients experienced statistically significant improvements in active pain and functionality score after the first treatment.
  • Additionally, patients experienced a mean decrease in resting pain after the first treatment, yet outcomes were not statistically significant until after the second treatment.
  • On average, patients experienced:
    • an 84.31% decrease in resting pain,
    • a 61.95% decrease in active pain,
    • and a 55.68% increase in functionality score at the final follow-up.
  • Patients also reported a mean 67% total overall improvement at study conclusion. Outcomes at the final follow-up after the fourth treatment were statistically significant compared to outcomes at baseline, after first treatment, after second treatment, and after third treatment.

In this study we concluded: “These results are promising, and additional research with a larger sample size and longer follow-up is needed to further examine the treatment effectiveness of multiple BMC injections for knee osteoarthritis.”


Recent research on bone marrow derived stem cell therapy

A February 2021 study, (5) citing our above research, among other research studies investigated the available literature on the use of bone marrow aspirate concentrate (BMAC) and summarize the current evidence supporting its potential for the stem cell injective treatment of joints affected by osteoarthritis. They noted that the “publication trend (of bone marrow aspirate concentrate research) remarkably increased over time. A total of 22 studies were included in the qualitative data synthesis: four preclinical studies and 18 clinical studies, for a total number of 4626 patients. Safety was documented by all studies, with a low number of adverse events. An overall improvement in pain and function was documented in most of the studies.” This study team concluded: “There is a growing interest in the field of bone marrow aspirate concentrate injections for the treatment of osteoarthritis, with promising results in preclinical and clinical studies in terms of safety and effectiveness. Nevertheless, the current knowledge is still preliminary. Preclinical research is still needed to optimize bone marrow aspirate concentrate use, as well as high-level large controlled trials to better understand the real potential of bone marrow aspirate concentrate injections for the treatment of patients affected by osteoarthritis.”

In the above study, the authors noted that there is a significant increase in the number of papers being produced. They like other researchers are looking for more because the treatment seems to work.

An August 2019 study, (6) which also cited our research paper said: “The available literature is undermined by both the lack of high-quality studies and the varied clinical settings and different protocols reported in the few random clinical trials presently published. . . Nevertheless, the use of (bone marrow aspirate concentrate) has been shown to be safe and have some short-term beneficial effects.” The treatment seems to work.

Regeneration of cartilage

A January 2020 (7) study from Loughborough University in the United Kingdom suggests:

“Pre-clinical studies have demonstrated successful, safe and encouraging results for articular cartilage repair and regeneration (with intra-articular injections of bone marrow derived mesenchymal stem cells). This is concluded to be due to the multilineage differential potential, immunosuppressive and self-renewal capabilities of bone marrow derived mesenchymal stem cells, which have shown to augment pain and improve functional outcomes.

Subsequently, clinical applications of intra-articular injections of bone marrow derived mesenchymal stem cells are steadily increasing, with most studies demonstrating a decrease in poor cartilage index, improvements in pain, function and Quality of Life; with moderate-to-high level evidence regarding safety for therapeutic administration . . .

Overall, the benefits of intra-articular injections of bone marrow derived mesenchymal stem cells were deemed to outweigh the adverse effects; thus, this treatment be considered as a future therapy strategy. To realize this, long-term large-scale randomized clinical trials are required to enable improved interpretations, to determine the validity of efficacy in future studies.”

A study published in the Archives of orthopaedic and trauma surgery (8) in August 2019 offered these observations on improved outcomes after mesenchymal stem cells injections for knee osteoarthritis: results at 12-months follow-up. This was a systematic review of 18 medical studies and 1069 knees offered treatment.

  • 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 investigators wrote: “According to the current evidences and the main findings of this systematic review, we reported that MSC infiltrations for knee osteoarthritis 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.”

A study in the journal Cytotherapy (9), examined the injection of mesenchymal stromal cells (bone marrow derived stem cells) as a treatment for knee osteoarthritis.

The study subjects were randomized into two groups:

  • A single injection of stem cells, or
  • A placebo injection of saline solution

Patients were followed up for 6 months after the injection.

Scores were recorded for :

  • Pain level and function improvements to include: walking distance, painless walking distance, standing time and knee flexion compared with the placebo group at 3 and 6 months

The conclusion of this research was the bone marrow derived stem cell injection demonstrated safety and effectiveness. However more research would be needed to confirm this.

Research: Bone marrow derived stem cell injection provided significant and clinically relevant pain relief over 6 months versus placebo.

In their 2016 study published in the journal Clinical and translational medicine,(10) researchers at Georgia Regents University wrote: “Current pharmacological treatment strategies are ineffective to prevent the osteoarthritic progression; however, cellular therapies have the potential to regenerate the lost cartilage, combat cartilage degeneration, provide pain relief, and improve patient mobility.” They add that among the cellular therapies, bone marrow-derived stem cells which have been shown to have a higher chondrogenic capability (the ability to make cartilage) than adipose (fat) derived stem cells, and they have been studied more extensively than the fat derived stem cells.

They also note that: “Due to the increasing incidence and prevalence of osteoarthritis, more innovative and effective therapeutic modalities need to be investigated, including MSCs. More randomized clinical trials need to be completed in order to demonstrate the efficacy, safety, and benefits of MSCs in treating patients with osteoarthritis.”

Doctors suggest that patients may experience benefits for at least two years

This is from a recent study published in the journal Experimental and therapeutic medicine. (11)

“MSC treatment in patients with knee osteoarthritis showed continual efficacy for 24 months compared with their pretreatment condition. Effectiveness of MSCs was improved at 12 and 24 months post-treatment, compared with at 3 and 6 months. . .  MSC application ameliorated the overall outcomes of patients with knee osteoarthritis, including pain relief and functional improvement from basal (base) evaluations, particularly at 12 and 24 months after follow-up.

This was after a single treatment only.

A July 2021 review study on Bone Marrow Aspirate Concentrate for the Treatment of Knee Osteoarthritis

A July 2021 paper (12) gave this assessment of Bone marrow aspirate concentrate (BMAC) for symptomatic knee osteoarthritis. They have good things to say and not so good things. First, how was the study conducted?

The study authors reviewed previously published research and found eight studies met their inclusion criteria, including a total of 299 knees with an average follow-up of 12.9 months.

  • Of all patient-reported outcomes assessed across studies, 34 of 36 patient reported (94.4%) demonstrated significant improvement from baseline to latest follow-up.
  • Five studies evaluating numerical pain scores (visual analog scale and Numeric Rating Scale) reported significant improvements in pain level at final follow-up.
  • However, 3 comparative studies evaluating Bone marrow aspirate concentrate in relation to other therapeutic injections failed to demonstrate the clinical superiority of Bone marrow aspirate concentrate.

Conclusion: “The Bone marrow aspirate concentrate injection is effective in improving pain and patient-reported outcomes in patients with knee osteoarthritis at short- to midterm follow-up. Nevertheless, Bone marrow aspirate concentrate has not demonstrated clinical superiority in relation to other biologic therapies commonly used in the treatment of osteoarthritis, including platelet-rich plasma and microfragmented adipose tissue, or in relation to placebo. The high cost of the Bone marrow aspirate concentrate injection in comparison with other biologic and nonoperative treatment modalities may limit its utility despite demonstrable clinical benefit.”

November 2021 research: Bone marrow concentrate vs. PRP vs. Hyaluronic acid

A study from November 2021 (13) offered a direct comparison of different biological knee pain treatments – Bone Marrow Aspirate Concentrate (stem cell therapy), Platelet-rich Plasma (PRP), or Hyaluronic acid (HA) for osteoarthritis treatment.

Patients with knee pain and osteoarthritis grade II to IV were randomized to receive a Bone Marrow Aspirate Concentrate , PRP, and Hyaluronic acid injection in the knee. Pain and function scores were used to establish a base line and standard comparison values to be used a values at one, three, six, nine, and 12 months.

Results: A total of 175 patients with a knee osteoarthritis KL grade II-IV were randomized; 111 were treated with BMAC injection, 30 with Hyaluronic acid injection, and 34 patients with PRP injection. There were no serious side effects.

The mean VAS (pain) scores (pain is measured 0= No pain to 10 =agonizing pan)  after three, seven, 14, and 21 days showed significant differences between groups with a drop of VAS in all groups but with a difference in the Bone Marrow Aspirate Concentrate group in comparison to other groups. There were high statistically significant differences between baseline scores and those after 12 months in the other pain and disability scores used to measure the outcomes.

The researchers found almost immediate pain relief after Bone marrow aspirate concentrate injections, with a trend of pain decrease over measured time (from 3 days after to 3 weeks). A drop in pain level was found among PRP and HA groups, but it was not as sharp as they found in the Bone marrow aspirate concentrate group.

  • Conclusions: Bone marrow aspirate concentrate,  Platelet Rich Plasma, and Hyaluronic acid injections are safe therapeutic options for knee o0steoarthritis and provide positive clinical outcomes after 12 months in comparison with findings preceding the intervention. Bone Marrow Aspirate Concentrate could be better in terms of clinical improvements in the treatment of knee osteoarthritis than PRP and Hyaluronic acid injection up to 12 months. PRP provides better outcomes than Hyaluronic acid injection during the observation period, but these results are not statistically significant.

Notes: Each patient received one treatment – In our office we have found in experience that whether being treated with PRP or bone marrow concentrate the answer to how many treatments will be needed is dependent on the level of your injury or degenerative condition and your goals of treatment. It is most common to need several treatments in order to heal. It is impossible to tell you how many treatments you will need. Most patients heal, and some do not. Everyone’s healing course is different. Rarely, a patient will have relief after one treatment. Some have no relief after several injections, and then may suddenly have pain relief. Stopping your injection series prior to healing will not assist healing. Treatments are generally scheduled every two weeks for fastest healing.

One injection of bone marrow stem cells versus one injection of Hyaluronic acid injections

In another November 2021 study (14), doctors performed a  double-blind randomized controlled trial to compare clinical improvement and radiographic findings up to 2 years of follow-up of a single intra-articular injection of bone marrow aspirate concentrate versus hyaluronic acid  for the treatment of knee osteoarthritis. The hypothesis was that bone marrow aspirate concentrate injection could lead to better clinical and radiographic results compared to viscosupplementation.

Methods: Patients with bilateral (both knees) knee osteoarthritis were randomized to one intra-articular injection of tibial (shin bone)-derived bone marrow aspirate concentrate in one knee and one hyaluronic acid injection in the other knee.

Patients were evaluated before the injection and at one, three, six, twelve, and 24 months with the IKDC (International Knee Documentation Committee) subjective score (which measures overall function score), VAS (Visual Analogue Scale 0 – 10) for pain, and the KOOS (Knee Injury and Osteoarthritis Outcome Score).


  • No severe adverse events nor differences were reported in terms of mild adverse events and treatment failures in bone marrow aspirate concentrate and hyaluronic acid groups.
  • The IKDC subjective score improved from baseline to all follow-ups for bone marrow aspirate concentrate. While in the hyaluronic acid group, improvement was seen up to 12 months but then decreased at 24 months .
  • Compared to hyaluronic acid, bone marrow aspirate concentrate showed a higher improvement for VAS pain at 12  and 24 months.

Conclusion: Bone marrow aspirate concentrate did not demonstrate a clinically significant superiority at short-term compared to viscosupplementation, reporting overall comparable results in terms of clinical scores, failures, adverse events, radiographic evaluation, MCID achievement, and patient treatment judgment. However, while hyaluronic acid results decreased over time, bone marrow aspirate concentrate presented more durable results in mild osteoarthritis knees.

Stem cell therapy, PRP therapy and a hyaluronate

In some practices stem cell therapy and PRP therapy are given at the same time. This is something that we typically do not do because of the platelets already present in the bone marrow concentrate. There is also extra cost involved to the patient that many times we do see as being justified. Many people however, do get great benefit from this combined treatment. Let’s explore a comparative study published in January 2021.(15)

The study aimed to determine the clinical response to an autologous bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) intra-articular injection compared to an active comparator  (Gel-One® crosslinked hyaluronate (HA)).

  • Participants with diagnosed knee osteoarthritis were divided into one of two treatment groups.
    • One group will receive bone marrow aspirate concentrate immediately followed by a PRP injection or a single injection of Gel-One® crosslinked hyaluronate (HA).
    • Outcomes were assessed at three, six, and 12 months post-treatment.
  • Results: Significant improvements were observed in both treatment groups for all Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales with the exception of the symptoms assessment at 12 months in the hyaluronate group. Results demonstrate that both treatment groups experienced clinically and statistically significant improvement across the KOOS subscales. While BMAC has shown promise in the treatment of knee osteoarthritis, there is a need for multi-center investigations with larger sample sizes, an extended follow-up, and placebo-based control.

One injection of bone marrow stem cells versus one injection of PRP

A January 2022 study (16) compared bone marrow derived stem cell therapy vs. PRP. I want to point out this is one shot vs one shot and the results were compared 12 months later. Typically we do not see patients achieve good results with a one-hot PRP treatment.

investigational cell therapies injected intra-articularly, such as bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP), have shown safety and therapeutic potency providing patients with pain relief. In the current retrospective comparative study, we investigated the differences in pain and functional improvements in patients with symptomatic knee osteoarthritis receiving intra-articular injections of BMAC vs PRP.

Pain and functionality scores were measured at baseline and at different time points post-injection over 12 months, using 3 self-administered, clinically validated questionnaires: the visual analogue scale (VAS) for assessing pain intensity, the knee injury and osteoarthritis outcome score (KOOS) for evaluating functionality and knee-related quality of life, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) for evaluating physical function.

The BMAC group significantly improved in VAS, KOOS, and WOMAC scores between baseline and 12 months (57.4, 75.88, and 73.95% mean score improvement, respectively). In contrast, the PRP group (n = 13 knees) witnessed nonsignificant improvement in all scores. BMAC, in comparison to PRP, induced significant improvement in outcomes by 29.38% on the VAS scale, 53.89% on the KOOS scale, and 51.71% on the WOMAC scale.

Conclusions: Intra-articular autologous BMAC injections are safe, effective in treating pain, and ameliorate functionality in patients with symptomatic knee osteoarthritis to a greater extent than PRP injections. Intra-articular autologous BMAC therapy is safe and provides more relief to patients with symptomatic knee osteoarthritis compared to PRP therapy.

Research:  Long-term safety and efficacy of adipose-derived mesenchymal stem cell therapy

In a June 2022 study (20), researchers assessed the benefit of stem cell therapy in the treatment of mild to severe knee osteoarthritis. From the study: “A total of 329 study participants with painful knee osteoarthritis undertook stem cell therapy and were followed up for two years. Stem cell therapy was well tolerated and safe. Significant pain and functional improvement were observed in all of the participant groups including those with severe bone-on-bone osteoarthritis. Participants’ age and weight did not influence the clinical outcome. This study shows that stem cell therapy is an effective, safe and long-lasting treatment for knee osteoarthritis and greatly reduces knee pain and improves the function of the knee. Stem cell therapy may delay or prevent knee replacement surgery and result in significant global health and economic benefit.”

A May 2022 study (21) examined the mid-term results of of adipose-derived derived stem cells. The research team writes: “Although successful short-term results of the intra-articular injection of mesenchymal stem cells (MSCs) for the conservative treatment of knee osteoarthritis (OA) have been reported, the mid-term results of the injection of adipose-derived MSCs remains unknown. (The researchers)  assessed the mid-term safety and efficacy of the intra-articular injection of adipose-derived derived stem cells in patients with knee osteoarthritis. Eleven patients with knee osteoarthritis were prospectively enrolled and underwent serial evaluations during a 5-year follow-up of a single intra-articular injection of autologous high-dose adipose stem cells. What the researchers found was “A single intra-articular injection of autologous, high-dose adipose-derived MSCs provided safe and clinical improvement without radiologic aggravation for 5 years. Furthermore, structural changes in the osteoarthritic knee showed significant improvement up to 3 years, suggesting a possible option for disease-modifying outpatient treatment for patients with knee osteoarthritis.”

Patches or injections?

Many patients have questions when it comes to stem cell therapy. One series of questions concerns the application of treatment. Stem cells can be added during a surgery, such as a bio-patch or scaffold coated with stem cells can be constructed to fill in cartilage lesions or holes.

In this April 2021 paper, (17) which cites our study, researchers summarized the question, patches or injections by answering, both treatments can work. This is what they published:

“The value of bone marrow aspirate concentrates for treatment of human knee cartilage lesions is unclear. Most of the studies were performed with intra-articular injections. However, subchondral bone plays an important role in the progression of osteoarthritis. We investigated by a literature review whether joint, subchondral bone, or/and scaffolds implantation of fresh autologous bone marrow aspirate concentrated (BMAC) containing mesenchymal stem cells (MSCs) would improve osteoarthritis. There is in vivo evidence that suggests that all these different approaches (intra-articular injections, subchondral implantation, scaffolds loaded with BMAC) can improve the patient.  . .”

It should also be pointed out that this research suggested scaffolds had a better long-term effect. This however was compared to single treatments or treatments halted at a specific point. In many cases of significant osteoarthritis a more aggressive injection treatment may be recommended.

Are bone marrow stem cells a better anti-inflammatory than cortisone injections?

A January 2022 paper (19) Osteoarthritis has generally been introduced as a degenerative disease; however, it has recently been understood as a low-grade chronic inflammatory process that could promote symptoms and accelerate the progression of osteoarthritis. Current treatment strategies, including corticosteroid injections, have no impact on the osteoarthritis disease progression. Mesenchymal stem cells (MSCs) based therapy seem to be in the spotlight as a disease-modifying treatment because this strategy provides enlarged anti-inflammatory and chondroprotective (cartilage protective) effects. . . MSCs exert immunomodulatory (management of immune response), immunosuppressive (suppresses the inflammatory response), antiapoptotic (prevents cell death), and chondrogenic (promotes cartilage growth) effects mainly by paracrine effect (the communication network where cells talk to each other).

Long-term effectives of stem cell therapy for knee osteoarthritis

“A December 2021 study in Journal of translational medicine (18) wrote: “Conventional treatments have demonstrated only modest clinical benefits whereas cell-based therapies have shown encouraging results, but important details, such as dose needed, long-term evolution or number of applications required are scarcely known. Here we have reanalyzed results from two recent pilot trials with autologous bone marrow-derived mesenchymal stromal cells . .  We find that cell doses of 10, 40 and 100 million autologous cells per knee provided quite similar healing results and that much of the effect attained one year after cell application remained after two and four years. These results are encouraging because they indicate that, apart from safety and simplicity: (i) the beneficial effect is both significant and sizeable, (ii) it can be achieved with a single injection of cells, and (iii) the effect is perdurable for years.”

Comparing different stem cell types to placebo studies.

A May 2022 study (22) from the California Institute of Behavioral Neurosciences & Psychology addressed the problem of while intraarticular stem cell therapy has become increasingly used to treat knee osteoarthritis, there is a minimal of high-quality evidence to support its use. In their study, researchers aimed to see how well intra-articular injections of mesenchymal stem cells (MSCs) worked and how safe they were for individuals with knee osteoarthritis.

In reviewing the clinical charts of 723 people who had participated in previous trials, the researchers isolated the experimental groups who received multipotent MSCs, mesenchymal progenitor cells (MPCs), adipose tissue progenitor stem cells (AD-MPCs), adipose tissue mesenchymal stem cells (AD-MSCs), bone marrow mesenchymal stem cells (BM-MSCs), bone marrow aspiration (BMA), bone marrow aspiration concentration (BMAC), or micro fragmented adipose tissue (MFAT) while the controlled groups received normal saline (NS), hyaluronic acid (HA), placebo, or went through conservative management. In conclusion, significant improvements were noticed in the MSCs groups via different outcome measuring tools. Furthermore, no significant adverse events have been observed. Therefore, intra-articular injections of MSCs are effective and safe in relieving pain and improving motor function in individuals with knee osteoarthritis in the short term, contrary to earlier research findings.

The effectiveness of a single Bone Marrow Aspirate Concentrate injection in the treatment of knee osteoarthritis

A July 2022 study (23) systematically reviewed published research to evaluate the efficacy of isolated Bone Marrow Aspirate Concentrate injection in the treatment of knee osteoarthritis. The study authors wrote: “The Bone Marrow Aspirate Concentrate injection is effective in improving pain and patient-reported outcomes in patients with knee osteoarthritis at short- to midterm follow-up. Nevertheless, Bone Marrow Aspirate Concentrate has not demonstrated clinical superiority in relation to other biologic therapies commonly used in the treatment of knee osteoarthritis, including platelet-rich plasma and microfragmented adipose tissue, or in relation to placebo. The high cost of the Bone Marrow Aspirate Concentrate injection in comparison with other biologic and nonoperative treatment modalities may limit its utility despite demonstrable clinical benefit.”

Our conclusions about bone marrow derived stem cells for knee osteoarthritis

Returning to our own published research cited above, I would like to recap the learning points:

  • We found that in the short-term, receiving multiple injections may be more effective than receiving a single Bone Marrow Concentrate stem cell injection.
    • Outcomes at the final follow-up after the fourth treatment were statistically significant compared with outcomes at baseline, after first treatment, after second treatment, and after third treatment.
  • Functionality score increased after first treatment, illustrating that patients experienced an immediate benefit in performing everyday activities with less difficulty.
  • By the second injection, patients began to report improvement with pain at rest. Patients then experienced additional decreases in resting pain with each treatment thereafter.
  • The increase in mean functionality score with successive BMC treatments shows that increasing the number of BMC treatments improves patient performance in daily activities.

The present findings may provide new clinical insights into treating osteoarthritis with Bone Marrow Concentrate. If Bone Marrow Concentrate treatments become more affordable or covered by insurance companies, there could be an increase in the number of patients receiving multiple Bone Marrow Concentrate treatments for osteoarthritis. If patients who reported improvement to a single injection received multiple, they may experience increased symptomatic relief such as the patients in our study. An additional finding illustrated that patients experienced a greater pain relief when injected with a high-nucleated cell count compared to a lower dose. Our study demonstrates that gradual increase in BMC injections in a short time period may be more effective than a single injection.

We do call on more research to help validate our findings as our small sampling case studies are not definitive.

Do you have questions? Ask Dr. Darrow

The majority of patients who receive stem cell treatment for their knee pain experience quick recovery and little to no adverse side effects. As with any injection there is the possibility of infection at the site that may include redness, pain and inflammation. The treatment maybe ineffective for some. Your doctor should fully discuss the pros and cons of this treatment with you before you receive any injections. Some patients may not be eligible based on certain risk factors.

A leading provider of stem cell therapy, platelet rich plasma and prolotherapy

PHONE: (800) 300-9300 or 310-231-7000


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14 Boffa A, Di Martino A, Andriolo L, De Filippis R, Poggi A, Kon E, Zaffagnini S, Filardo G. Bone marrow aspirate concentrate injections provide similar results versus viscosupplementation up to 24 months of follow-up in patients with symptomatic knee osteoarthritis. A randomized controlled trial. Knee Surgery, Sports Traumatology, Arthroscopy. 2021 Nov 12:1-0.
15 Ruane JJ, Ross A, Zigmont V, McClure D, Gascon G. A Single-Blinded Randomized Controlled Trial of Mesenchymal Stem Cell Therapy for the Treatment of Osteoarthritis of the Knee with Active Control. Journal of Stem Cells & Regenerative Medicine. 2021;17(1):3.
16 El-Kadiry AE, Lumbao C, Salame N, Rafei M, Shammaa R. Bone marrow aspirate concentrate versus platelet-rich plasma for treating knee osteoarthritis: a one-year non-randomized retrospective comparative study. BMC Musculoskeletal Disorders. 2022 Dec;23(1):1-4.
17 Hernigou J, Vertongen P, Rasschaert J, Hernigou P. Role of Scaffolds, Subchondral, Intra-Articular Injections of Fresh Autologous Bone Marrow Concentrate Regenerative Cells in Treating Human Knee Cartilage Lesions: Different Approaches and Different Results. International journal of molecular sciences. 2021 Jan;22(8):3844.
18 Lamo-Espinosa JM, Prósper F, Blanco JF, Sánchez-Guijo F, Alberca M, García V, González-Vallinas M, García-Sancho J. Long-term efficacy of autologous bone marrow mesenchymal stromal cells for treatment of knee osteoarthritis. Journal of translational medicine. 2021 Dec;19(1):1-4.
19 Kwon DG, Kim MK, Jeon YS, Nam YC, Park JS, Ryu DJ. State of the art: the immunomodulatory role of MSCs for osteoarthritis. International Journal of Molecular Sciences. 2022 Jan 30;23(3):1618.
20 Freitag J, Wickham J, Shah K, Tenen A. Real-world evidence of mesenchymal stem cell therapy in knee osteoarthritis: a large prospective two-year case series. Regenerative Medicine. 2022 Mar(0).
21 Kim KI, Lee WS, Kim JH, Bae JK, Jin W. Safety and Efficacy of the Intra-articular Injection of Mesenchymal Stem Cells for the Treatment of Osteoarthritic Knee: A 5-Year Follow-up Study. Stem Cells Translational Medicine. 2022 May 14.
22 Shoukrie SI, Venugopal S, Dhanoa RK, Selvaraj R, Selvamani TY, Zahra A, Malla J, Hamouda RK, Hamid PF. Safety and Efficacy of Injecting Mesenchymal Stem Cells Into a Human Knee Joint To Treat Osteoarthritis: A Systematic Review. Cureus. 2022 May 8;14(5).
23 Keeling LE, Belk JW, Kraeutler MJ, Kallner AC, Lindsay A, McCarty EC, Postma WF. Bone marrow aspirate concentrate for the treatment of knee osteoarthritis: a systematic review. The American Journal of Sports Medicine. 2021 Jul 8:03635465211018837.




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