Does Stem Cell Therapy Actually Work?

It is the first question most patients ask. Answering it well takes understanding what stem cells actually do in the body, knowing which orthopedic conditions have been studied, and looking at what the published medical literature has shown to date. The sections below walk through each in order.

What Is Stem Cell Therapy

Stem cells researched in orthopedics are mesenchymal stem cells, also called mesenchymal stromal cells or mesenchymal signaling cells (MSCs). They are found throughout the body and are being evaluated for possible anti-inflammatory, immunomodulatory, and regenerative properties, along with anti-scarring, antimicrobial, and anti-oxidative effects.¹

Researchers describe two broad mechanisms:¹

• Differentiation. They can develop into different tissue types.
• Paracrine signaling. They release bioactive molecules, including exosomes, that signal to neighboring cells. These signals are described in the literature as helping to maintain tissue, limit further cell damage, moderate inflammation, recruit other cells to the area, and support repair.¹

Paracrine signaling is a major focus of research involving joints, tendons, and ligaments.

Stem cell therapies fall into three general categories:

Category	What it is	Common sources
Autologous	Uses the patient’s own tissue	Bone marrow aspirate concentrate (BMAC), microfragmented adipose tissue (MFAT)
Allogeneic	Uses donor-derived tissue	Umbilical cord (Wharton’s jelly), amniotic/placental tissue, amniotic fluid, donor bone marrow, donor fat
Culture-expanded	Uses autologous and allogeneic cells grown in a laboratory to reach higher, standardized cell counts	Laboratory expansion of donor-derived cells

Depending on the type of stem cell therapy, the biologic composition of the therapy may differ thus, providing another variable to consider when researching the use of stem cells in orthopedics., 

Why Patients Are Seeking Stem Cell Therapy

Interest has grown steadily, and the reasons patients seek therapy may include:

• Avoiding or delaying a surgery that has been recommended to them
• Persistent joint, tendon, or other soft tissue pain that has not responded to physical therapy, medication, or anti-inflammatory medications
• Supporting healing during recovery from surgery
• Addressing a problem early in order to prevent further injury progression
• Wanting a therapy that works with the body’s own repair processes rather than removing or replacing tissue

Older patients with arthritis, weekend athletes with a tendon injury, and professional athletes trying to perform with pain often have different goals but a similar underlying question: what can be done naturally to stay active and pain-free?

Why Physicians and Researchers Are Interested

Researchers have been studying stem cells since the 1960s, and its use has expanded into fields including orthopedics, wound healing, autoimmune and inflammatory disease, and recovery and longevity applications.¹

Applications of stem cells in orthopedics have focused on both acute and chronic musculoskeletal injuries. Tissues like cartilage, tendon, and ligaments have limited blood supply and a limited capacity to repair themselves. The research hypothesis is that stem cell therapies may reduce inflammation and initiate a healing cascade that could assist in tissue repair.¹ This is why musculoskeletal conditions are one of the most active areas of stem cell research with knee osteoarthritis being studied the most.

What the Research Shows for Knee Osteoarthritis

Knee osteoarthritis (OA) is the most heavily studied orthopedic application of stem cell therapy with available randomized controlled data.

A 2025 meta-analysis in Stem Cell Research and Therapy examined 8 randomized controlled trials and 502 patients with unoperated knee OA who received stem cell injections alone. Compared to control groups, patients showed statistically significant improvement in pain and function scores (WOMAC) at both 6 and 12 months.² Adverse event rates did not differ significantly from controls.

Separately, a 2025 Cochrane review (CD013342), a widely used framework for evidence synthesis, analyzed 25 randomized trials totaling 1,341 participants. Focused on the eight trials that compared stem cell injection directly against a placebo injection, the findings were:³

• Pain (0 to 10 scale): 1.2 points better with stem cell injection than placebo at six months.
• Function (0 to 100 scale): 14.2 points better with stem cell injection than placebo.
• Reported outcomes: 68 percent of stem cell patients reported a successful outcome, versus 53 percent with placebo.

There are some limitations interpreting this data. The trials used different cell types, preparation methods, and doses, so the results describe the category broadly rather than any single approach.

Other Orthopedic Conditions Under Study

Beyond the knee, stem cell therapy has been studied for a range of orthopedic conditions, including:⁶

• Joint osteoarthritis and chondromalacia
• Rotator cuff tears
• Shoulder and hip labral tears
• Tennis elbow and golfer’s elbow
• Patellar and hamstring tendinopathy and tears
• Achilles tendinopathy and tears
• Meniscus tears
• Ligament sprains and partial tears

The published research in these areas continues to grow.

Clinical Considerations

No single therapy fits every patient. In clinical practice, several considerations are commonly reviewed before stem cell therapy is discussed.

Establishing the diagnosis. Knee pain can originate from cartilage wear, a meniscus tear, a tendon, or maltracking of the kneecap. A diagnosis established through history taking, physical examination, and imaging comes before any discussion of which biologic may be considered.

Understanding functional goals. Correlating goals with the current physical findings will help create a plan of care and understand which biologic therapy may be appropriate. 

Post-injection protocols. A structured rehabilitation plan following the injection is commonly included in the overall plan of care, and follow-up evaluations allow the physician to determine whether additional therapy should be considered. Being able to adhere and participate in the prescribed plan of care is part of determining the next steps with therapy.

Looking Ahead

Stem cell and biologic therapies represent a growing area of orthopedic medicine.

In December 2024, the first mesenchymal stem cell therapy, Ryoncil (remestemcel-L-rknd), was approved for children two months and older with steroid-refractory acute graft-versus-host disease.⁴ It is the first approval of its kind and a meaningful signal for the field as a whole.

Research activity continues to expand across a wide range of conditions.

In orthopedics, researchers continue to investigate differences between cell sources, determine optimal dosing, and identify which patient populations may benefit most from future clinical trials.

Dr. Steve Yoon is a sports medicine and regenerative medicine physician in Los Angeles. He serves as Head Team Physician for the LA Clippers and Team Physician for the Los Angeles Angels, and has practiced in regenerative medicine for over 15 years.You can contact him here: https://www.steveyoonmd.com/contact/ 

Frequently Asked Questions

Does stem cell therapy actually work?

For knee osteoarthritis, randomized trials show improvement in pain and function compared with placebo.^2,3 Research in other orthopedic areas continues to grow. 

Which conditions has stem cell therapy been studied for most?

Knee osteoarthritis has by far the largest randomized trial base.^2,3 Hip and shoulder osteoarthritis, rotator cuff and other tendon injuries, and ligament injuries are also active areas of clinical research.⁶

What should I ask my physician?

Important questions to ask include which type of stem cell therapy is recommended, what outcomes have been observed in previous patients, whether imaging guidance will be used during the injection, and what to expect after the procedure.

References

1. Han, X., et al. (2025). Mesenchymal stem cells in treating human diseases: Molecular mechanisms and clinical studies. Signal Transduction and Targeted Therapy. https://doi.org/10.1038/s41392-025-02313-9

2. Cao M, Ou Z, Sheng R, et al., “Efficacy and safety of mesenchymal stem cells in knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials,” Stem Cell Research & Therapy, 16, 122 (2025).

3. Whittle SL, Johnston RV, McDonald S, et al., “Stem cell injections for osteoarthritis of the knee,” Cochrane Database of Systematic Reviews, 2025, Issue 4, Art. No. CD013342.

4. U.S. Food and Drug Administration, “FDA Approves First Mesenchymal Stromal Cell Therapy to Treat Steroid-Refractory Acute Graft-versus-Host Disease,” December 18, 2024.

5. Fang WH, Chen XT, Vangsness CT Jr. “Ultrasound-Guided Knee Injections Are More Accurate Than Blind Injections: A Systematic Review of Randomized Controlled Trials.” Arthroscopy, Sports Medicine, and Rehabilitation. 2021;3(4):e1177-e1187. doi:10.1016/j.asmr.2021.01.028

6. Goulian AJ, Goldstein B, Saad MA. “Advancements in Regenerative Therapies for Orthopedics: A Comprehensive Review of Platelet-Rich Plasma, Mesenchymal Stem Cells, Peptide Therapies, and Biomimetic Applications.” Journal of Clinical Medicine. 2025;14(6):2061. doi:10.3390/jcm14062061