Clinical Trials on Stem Cells for Orthopedic Healing

Stem cell therapy is changing how orthopedic injuries are treated. Unlike other methods that focus on short-term relief, stem cells aim to repair damaged tissues, offering hope for conditions like knee arthritis, back pain, and tendon injuries. Here's what you need to know:

• Pain Relief and Recovery: Trials show stem cells can reduce pain and improve function in conditions like knee osteoarthritis (up to 95% success) and Achilles tendinopathy (80% success).
• Long-Term Benefits: Stem cells outperform corticosteroids over time, offering sustained relief and delaying surgeries.
• Safety: Minimal risks, with side effects like swelling and pain resolving in weeks. No major complications have been reported.
• Sources and Methods: Bone marrow, fat, and umbilical cord cells are used. Treatments include injections or surgical implantation.
• Challenges: High costs and lack of standardization slow adoption, but "off-the-shelf" products and newborn stem cell banking are making progress.

Stem cells may reshape orthopedic care by focusing on tissue repair rather than just symptom management. However, more trials are needed to refine techniques and make treatments widely available.

Recent Clinical Trials and Results

Large-scale studies conducted from 2019 to 2025 have shed light on both the potential and the challenges of stem cell therapy in orthopedic care. Below, we’ll dive into the outcomes for specific conditions and how these treatments stack up against traditional options.

Treatment Results for Specific Orthopedic Conditions

Stem cell therapy has been explored for numerous orthopedic issues, with varying degrees of success:

• Knee osteoarthritis: A four-year study (2019–2022) by the Institute for Regenerative Medicine in Graz, Austria, followed 29 patients (37 knees) with severe osteoarthritis treated with bone marrow aspirate concentrate (BMAC). The results were impressive: a 95% success rate in pain relief and improved function, with none of the patients requiring knee replacement during the study period.
• Achilles tendinopathy: A Phase IIa trial conducted in 2024 showed promising results, with an 80% success rate at 24 weeks. Patients experienced less pain and imaging revealed a 0.8 mm reduction in tendon thickness.
• Lumbar facet arthropathy: A Phase 1 trial (NCT04410731) at the Mayo Clinic focused on treating chronic back pain with 10 million allogeneic MSCs per joint. At 24 months, 66.7% of participants maintained a ≥50% reduction in pain, and 55% showed reduced joint degeneration.
• Rotator cuff repairs: Trials comparing surgery alone to surgery combined with adipose-derived MSCs highlighted the benefits of stem cell therapy. The retear rate was 14.3% with stem cells, compared to 28.5% without.

Stem Cell Therapy Compared to Traditional Treatments

While these results highlight the potential of regenerative medicine, direct comparisons with traditional treatments offer a fuller picture of its role in orthopedic care.

The most extensive head-to-head comparison, the MILES study, involved 480 patients across four sites, including Duke and Emory, between March 2019 and June 2021. Led by Dr. Blake Boggess at Duke, the study evaluated three types of stem cell treatments (BMAC, SVF, and umbilical cord tissue) against corticosteroid injections for knee osteoarthritis. Surprisingly, none of the stem cell therapies outperformed corticosteroids in pain reduction at the 12-month mark. All groups showed improvement, but the costly stem cell treatments did not offer a clear advantage over standard injections in the first year.

"Physicians can help to create the conditions, but it's our own bodies that do the work of healing. We were hoping that using stem cells would aid in that process, but we were surprised to find that no option was better than the other." - Blake Boggess, DO, Principal Investigator, Duke University

However, the long-term data paints a different picture. Over two to four years, stem cell therapy has demonstrated more sustained benefits compared to corticosteroids, which typically provide relief for only about three months. For knee osteoarthritis, BMAC injections outperformed exercise therapy alone at the 24-month mark. In cases of corticosteroid-related osteonecrosis, subchondral BMAC injections achieved results comparable to total knee replacement after 12 years, offering a less invasive alternative to major surgery.

The safety profile for stem cell therapy has been consistently positive across all trials. No serious adverse events or infections were reported, and minor side effects like joint swelling, localized pain, and bruising resolved within a week.

Stem Cell Sources and Methods Used in Orthopedic Trials

Types of Stem Cells and Their Applications

Mesenchymal stem cells (MSCs) are at the forefront of orthopedic research due to their ability to transform into bone, cartilage, and fat cells - essential for repairing damaged joints and tissues. A review of 449 clinical trials revealed that bone marrow was the most commonly used source (26.5%), followed by adipose tissue (20.5%) and umbilical cord (15.4%).

Each source has unique characteristics. Bone marrow MSCs are harvested through an invasive bone puncture, often from the iliac crest. In contrast, adipose-derived cells are extracted via liposuction. Umbilical cord blood and tissue, collected non-invasively at birth, are gaining popularity as "off-the-shelf" options. These cells can be banked, expanded in labs, and used for multiple patients with a lower chance of rejection.

"Among the variously sourced MSCs, human umbilical cord blood-derived MSCs (hUCB-MSCs) have advantages of non-invasive cell collection, high capacity for expansion, and low immunogenicity for therapeutic applications as an off-the-shelf allogeneic product." - Nature Scientific Reports

The number of cells used in trials can vary widely, ranging from 500,000 to 970 million cells. Common doses include 10 million cells (8.2% of trials) and 20 million cells (8.0% of trials). Osteoarthritis of the hip and knee is the most frequent target condition, accounting for 37.6% of all stem cell trial applications. These diverse sources and applications pave the way for exploring different delivery methods in orthopedic treatments.

How Stem Cells Are Delivered in Treatment

There are two main ways doctors deliver stem cells to damaged joints and tissues. Intra-articular injections, guided by ultrasound or fluoroscopy, inject cells directly into joints to reduce inflammation and encourage repair.

For more complex cases requiring structural repair, surgical implantation is often used. In these procedures, stem cells are combined with a gel carrier, such as sodium hyaluronate, and implanted directly into drilled bone areas to promote integration. A notable example is Cartistem®, developed by MEDIPOST Co. Ltd. and approved in South Korea in January 2012. This product uses 5 million umbilical cord blood-derived MSCs per milliliter combined with hyaluronate gel. Between April 2019 and May 2021, patients treated with Cartistem® showed significantly better pain scores (15.21 vs. 28.57) at 24 months compared to traditional microdrilling.

Other approaches include same-day procedures like bone marrow aspirate concentrate (BMAC), where cells are harvested and processed within hours, and culture-expanded products, which involve growing cells in a lab for several weeks before cryopreservation. Some treatments also enhance the healing environment by combining stem cells with platelet-rich plasma or bone morphogenetic proteins.

The Role of Cord Blood and Tissue Banking

Banking newborn stem cells offers families a long-term source of potent MSCs that can be stored for decades. These cells can be used later for orthopedic conditions, providing a distinct advantage over cells harvested in adulthood. Companies like Americord Registry offer services to preserve cord blood, cord tissue, and placental tissue, all of which are rich in MSCs frequently used in orthopedic trials.

The benefits of banked cord cells become apparent when compared to cells harvested later in life. Bone marrow or fat-derived cells from older individuals may lose their regenerative capacity due to aging. In contrast, cord-derived cells, preserved at birth, retain their full potential. These cells also eliminate the need for invasive harvesting procedures and ensure standardized, quality-controlled doses for future treatments.

With regulatory approvals expanding - such as India’s approval of StemOne® for knee osteoarthritis in September 2022 - the value of banked stem cells continues to grow. Americord Registry (https://americordblood.com) provides advanced preservation options, ensuring families have access to high-quality regenerative cells for emerging orthopedic therapies. By preserving these cells at birth, families can prepare for future treatments without the limitations of aging autologous cells.

Safety and Risks in Stem Cell Therapy

Common Side Effects and Complications

Stem cell therapy has shown promising results in orthopedic treatments, but ensuring its safety is essential. A review of 1,924 patients revealed a 12.3% occurrence of short-term side effects such as swelling, pain at the injection site, joint discomfort, and reduced mobility. These symptoms typically resolved within four weeks. Another analysis involving 2,372 patients showed a serious adverse event rate of 1.5% (0.7 per 100 person-years), with 3.9% reporting post-procedure pain and 3.8% experiencing pain from worsening joint conditions.

"Treatment of knee OA with autologous mesenchymal stem cell injections poses no risk of major complications (infection, sepsis, neoplasm, embolism, or death) and poses moderate risk of swelling and pain at the injection site lasting less than 4 weeks." - Clara Riggle, BS

Concerns about cancer risks have been largely theoretical. Long-term monitoring of 2,372 patients identified only 7 cases of neoplasms (0.3%), which is notably lower than the general U.S. population's annual cancer incidence of 0.44%. However, studies beyond 24 months are necessary to fully understand potential long-term risks.

These findings highlight the importance of evaluating how different stem cell sources impact safety outcomes.

Safety Differences Between Stem Cell Sources

The source of stem cells plays a significant role in the likelihood of adverse events, making it crucial to assess each source individually. Umbilical cord-derived cells have the highest rate of temporary side effects at 51.7%, mainly joint swelling and fluid buildup. For instance, a Phase 3 trial reported joint swelling in 24.1% of patients treated with umbilical cord tissue, compared to just 7.4% in the corticosteroid control group. Cultured adipose-derived cells showed an adverse event rate of 29.5%.

Bone marrow-derived stem cells appear to have a more favorable safety record, with adverse event rates around 10.7%. On the other hand, the stromal vascular fraction (SVF) from adipose tissue has a lower overall adverse event rate of 8.1%, but a higher rate of post-procedural bruising - 38.6% in one study. A multicenter trial conducted between March 2019 and June 2021 revealed that patients treated with SVF had substantially more bruising compared to those receiving bone marrow-derived stem cells, which had a bruising rate of 12.2%.

Stem Cell Source	Adverse Event Rate	Common Side Effects
Umbilical Cord	51.7%	Joint swelling, arthralgia, effusion
Adipose (Cultured)	29.5%	Swelling, pain lasting <4 weeks
Bone Marrow	10.7%	Injection site pain, minor swelling
SVF (Adipose)	8.1%	Contusion, hematoma, joint pain

Stem cell injections generally compare well to conventional treatments. For example, their adverse event rate of about 12.3% is significantly lower than the 27.7% rate seen with hyaluronic acid injections and is roughly on par with corticosteroid injections at 14.3%. Most side effects are linked to the injection process rather than the stem cells themselves, underscoring the importance of skilled application and strict adherence to sterile techniques.

Future Directions in Stem Cell Research for Orthopedics

New Clinical Trials and Expanded Applications

Stem cell research is moving beyond knee osteoarthritis, with clinical trials now targeting conditions like lumbar facet arthropathy (LFA), which affects 15% to 45% of patients with back pain. For example, the CellKine Phase I trial in Jacksonville delivered 10 million allogeneic bone marrow-derived stem cells to 10 patients with LFA, paving the way for Phase II studies (NCT06001853).

Another area of focus is chronic Achilles tendinopathy. At the Royal National Orthopaedic Hospital, a Phase IIa study treated 10 patients with autologous bone marrow-derived stem cell injections (median dose: 12.2×10^6 cells). After 24 weeks, 80% of participants reported a pain and function score improvement of over 12 points.

"The pain responder rate, defined as a ≥ 50% reduction in VAS scores, increased from 33.33% at 3 months to 75% at 6 months and sustained at 66.67% at 12, 18, and 24 months post-treatment." - Stem Cell Research & Therapy

Researchers are also shifting toward "off-the-shelf" allogeneic products, which offer cost savings and logistical ease for large-scale use. Trials are testing repeated dosing protocols to sustain therapeutic effects. For instance, at Army Medical University, 14 patients with knee osteoarthritis received four weekly injections of 15 million umbilical cord-derived stem cells. This approach improved average WOMAC scores from 26.0 to 8.5 in just three months. These advancements are laying the groundwork for integrating new technologies to enhance treatment outcomes.

New Technologies in Stem Cell Therapy

Emerging technologies are poised to refine stem cell therapies further. Biomimetic scaffolds, designed to mimic natural tissue properties, are being developed to provide structural support that encourages cell adhesion and growth. These scaffolds can be paired with growth factors like TGF-β and BMPs to amplify regenerative effects.

Gene editing and induced pluripotent stem cells (iPSCs) are also gaining traction. By reprogramming adult cells with transcription factors like Oct-4, SOX2, KLF4, and c-MYC, researchers can create therapies tailored to individual patients while reducing the risk of immune rejection.

"The integration of cutting-edge techniques like 3D printing and gene therapy could further revolutionise orthopaedic regenerative medicine." - Moh. Tawhidul Islam, New Vision University

Another promising area is cell-free therapies, which harness the stem cell "secretome" - extracellular vesicles and exosomes that deliver regenerative benefits without the risks tied to live cell transplantation. Companies like Americord Registry are even offering exosome banking alongside cord blood and tissue preservation, providing families with future access to these emerging treatments.

Regulatory Approval and Clinical Availability

As trial results improve, regulatory frameworks are adapting to accommodate these therapies. Stem cell treatments are classified as Advanced Therapy Medicinal Products (ATMPs), subject to stringent oversight by agencies like the FDA, EMA, and MHRA. However, progress has been slow - of 449 clinical trials for mesenchymal stem cell injections in orthopedics, only 35.4% have been completed, and just 12.5% have published results in peer-reviewed journals.

The average trial takes 40.6 months, with some extending up to 153 months. A major hurdle is the variability in protocols - researchers have identified at least eight different cell sources and over 50 dosage schemes, complicating efforts to establish standardized safety benchmarks. Alarmingly, 55.5% of trial protocols fail to specify the cell concentration used.

"Any human treatment involving cell-based products is considered an advanced therapies medicinal product (ATMP), with strict regulatory requirements." - Nature

The proliferation of unapproved "stem cell clinics" has further muddied the regulatory landscape, prompting stricter enforcement from agencies. For legitimate therapies to reach broader clinical use, researchers must complete lengthy multi-phase trials akin to the process for new pharmaceuticals. The timeline for widespread availability will hinge on standardization efforts and the successful completion of large-scale Phase III trials.

Conclusion

Stem cell therapy is reshaping the way orthopedic healing is approached. Unlike traditional methods focused on pain relief or delaying surgery, this therapy works to restore tissue structure and function. Instead of just masking symptoms, it offers the potential to regenerate damaged tissue and improve joint functionality. Clinical data backs this up, with meta-regression analysis showing that MSC therapy significantly reduces pain (β = 8.45, p < 0.05).

The future of orthopedic regenerative medicine is evolving rapidly, thanks to these promising results. Clinical trials consistently highlight a strong safety profile, with no serious procedure-related adverse events reported. While studies like MILES found that stem cells provided similar pain relief to corticosteroids after one year, the defining advantage of stem cell therapy lies in its potential for structural tissue repair - a capability that traditional treatments lack.

However, challenges remain. Researchers are working to standardize treatment protocols, refine dosing strategies, and validate long-term results through large-scale Phase III trials. The shift toward allogeneic "off-the-shelf" stem cell products, derived from young and healthy donors, is making these therapies more accessible and affordable. Additionally, services like Americord Registry offer storage options for high-quality stem cells from sources like cord blood, cord tissue, and placental tissue, ensuring future access to cutting-edge regenerative treatments.

Integrating stem cell technologies into orthopedic care has the potential to significantly improve patient outcomes. It could also help reduce the staggering $60 billion annual cost of osteoarthritis in the U.S. and address unmet needs in musculoskeletal care. As regulations evolve and new trials explore applications beyond knee osteoarthritis, the next few years will reveal how quickly these therapies can become a standard part of clinical practice.

FAQs

What are the benefits of stem cell therapy for orthopedic injuries?

Stem cell therapy brings several benefits for treating orthopedic injuries. It can aid tissue repair, reduce inflammation, and alleviate pain. This approach often uses mesenchymal stem cells, which have shown the ability to help regenerate damaged cartilage, tendons, and ligaments - issues commonly seen in conditions like osteoarthritis or sports-related injuries.

What makes this treatment stand out is its minimally invasive nature, offering an alternative to surgery. For many patients, it may even delay or eliminate the need for procedures like joint replacements. Beyond simply managing symptoms, stem cell therapy focuses on restoring the structure and function of damaged tissues, aiming for long-lasting recovery and a better quality of life. With ongoing research, this method continues to reshape the possibilities in orthopedic care.

How do stem cell treatments compare to traditional options like corticosteroid injections for orthopedic conditions?

Stem cell treatments for orthopedic conditions, such as knee osteoarthritis, have gained attention for their potential. However, current evidence shows they deliver results similar to traditional treatments like corticosteroid injections. Research indicates that while stem cell therapies may help alleviate pain and improve function, their effects often align with placebo responses and offer no clear advantage over corticosteroids in slowing disease progression or enhancing long-term outcomes.

Corticosteroids continue to be a dependable option for symptom management. As for stem cell therapies, more studies are needed to fully understand their safety and long-term effectiveness. Although they represent an exciting frontier in regenerative medicine, they are not yet a proven alternative to conventional approaches.

What are the risks and side effects of stem cell therapy for orthopedic conditions?

Stem cell therapy offers potential as a treatment for orthopedic conditions, but it’s important to acknowledge that, like any medical procedure, it comes with risks and possible side effects. While most clinical trials report no serious complications, questions about long-term safety remain. Rare risks include infection, immune system reactions, or unintended tissue growth, particularly when treatments are not administered properly.

Research on conditions such as knee osteoarthritis and tendon injuries indicates that autologous stem cell treatments - those using the patient’s own cells - tend to be safe. However, since stem cell therapy is still a developing field, continued studies are crucial to better understand and reduce potential risks. If you’re thinking about pursuing this treatment, it’s vital to consult a qualified healthcare provider to determine if it’s a suitable option for your condition.