More than 600 million people suffer from osteoarthritis—a progressive, degenerative joint disorder resulting in cartilage damage, loss of joint function, and chronic pain.1 Treatments are often ineffective, as they aim to manage pain rather than address cartilage damage. In many cases, patients must undergo joint replacement surgery as a last resort.
Women bear 60 percent of the osteoarthritis burden, and this rate increases after menopause.2 In a biological sense of irony, a potential regenerative therapy comes from a source that postmenopausal women can’t produce—menstrual blood.
In a recent study published in Scientific Reports, researchers found that bioactive molecules from menstrual blood stem cells promoted cartilage regeneration in cultured cells and in human damaged cartilage samples, presenting a potential non-invasive treatment avenue for osteoarthritis.3
Menstrual Blood is a Source of Stem Cell Extracellular Vesicles
Menstrual blood is rich in mesenchymal stromal cells, which are stem cells that can generate bone, cartilage, blood vessels, and lymphatics.4 “These cells are very active because they rebuild endometrial lining every month in women, so their activeness can also stimulate other tissue cells to regenerate,” said Ilona Uzieliene, a stem cell researcher at the Innovative Medicine Center and coauthor of the study.
Ilona Uzieliene, a stem cell researcher at Kaunas University of Technology and Innovative Medicine Center discovered that menstrual blood-derived stem cells can regenerate cartilage.
Ilona Uzieliene
Another advantage of menstrual blood is that researchers can obtain samples non-invasively, compared to sources like bone marrow that require invasive procedures. Importantly, menstrual blood samples can be obtained consensually, which bypasses ethical issues that stem cell researchers face while working with embryonic stem cells.
Uzieliene’s team collected period blood from three healthy donors and isolated mesenchymal stromal cells from the purified samples. From the secretions of these cells, they isolated extracellular vesicles (EVs), which are “small particles in the nanometer range that contain lipids, proteins, microRNAs, and cytosolic or nuclear proteins,” explained Divyesh Joshi, an associate research scientist studying cardiovascular biology at Yale University who was not involved in the new study.
EVs perform important functions like cellular communication, immune roles, and crucially, tissue repair and regeneration.5
Uzieliene’s team cultured chondrocytes—the only cells in cartilage—and treated them with EVs from menstrual blood stromal cells. They found that the treated chondrocytes were not only able to uptake the vesicles, but also regenerate cartilage components.
Building Back Cartilage with Menstrual Blood EVs
Cartilage is composed of a dense scaffolding called the extracellular matrix (ECM), which is produced by chondrocytes. The ECM consists of proteoglycans which preserve the biomechanical properties of cartilage.6 Additionally, a lubricant fluid bathes the cartilage to absorb shock and prevent damage.
“During osteoarthritis, the lubricant becomes loaded with pro‑inflammatory and death‑signaling molecules,” explained Dimitrios Kouroupis, a regenerative medicine researcher at the University of Miami and who was not associated with the new study. “The cartilage is continuously bathed in this ‘bad’ lubricant, and over time the chondrocytes become apoptotic, ECM breaks down, leading to loss of structural integrity of cartilage.”
In the study, Uzieliene’s team used a 3D cell culture system to mimic the human cartilage tissue environment. In this system, chondrocytes treated with EVs from menstrual blood stromal cells synthesized more of the ECM compared to untreated controls. The treated chondrocytes also exhibited increased proteoglycan levels.
Could this treatment work in the native environment of human tissue? To address this, Uzieliene’s team obtained damaged cartilage tissue discarded as waste during patients’ cartilage replacement surgeries. To these tissue explants, the team added a pro-inflammatory molecule that exacerbates ECM loss. Upon adding EVs from menstrual blood stromal cells to tissue explants in this inflammatory context, the ECM loss was notably reduced.
Pointing out that the cartilage explants were from patients with advanced osteoarthritis, Kouroupis said, “The fact that they still see a clear beneficial effect of the vesicles on such severely damaged tissue is very, very important.”
In addition to reducing ECM loss, EV-treated chondrocytes also over-expressed cartilage-specific genes, along with increased expression of chemical signals like interleukin (IL) 6. These results indicate a coordinated improvement of ECM synthesis through multiple mechanisms.
However, this presented a mechanistic black box to Joshi. “The big weakness is that we still don’t know what is doing the job inside these vesicles, and because they only look at cytokines like IL-6 at one time point, it’s very hard to say whether the vesicles are truly resolving inflammation or just changing its timing,” he said.
A Potential Cell-Free Therapy for Osteoarthritis
The researchers view this study as the starting point for developing a cell-free therapy for osteoarthritis, where secreted factors of stem cells, such as EVs, are used instead of stem cells themselves. “Cell-free therapies are the next big thing,” said Joshi. “[They] have a huge advantage, in that they have a high turnover. You don’t want a foreign entity to stay in the tissue forever, which could later turn cancerous.”
Other advantages include easier dosage adjustment and avoiding graft rejections.
“In the next five years, we’re going to see cell‑free EV therapies really take off, with multiple products reaching the clinic for musculoskeletal conditions, including osteoarthritis,” added Kouroupis.
Uzieliene, presenting a balanced view, said, “We are still at the beginning of this approach, but I’m hopeful that we will see results in the future.” It may even lead to personalized medicine, she added. “If women store their menstrual blood when young, they may be able to use it later for treating diseases.”
- Wang Z, et al. Global, regional and national burden of osteoarthritis in 1990-2021: a systematic analysis of the global burden of disease study 2021.BMC Musculoskelet Disord. 2024;25:1021.
- Xu H, et al. Global burden of osteoarthritis among postmenopausal women in 204 countries and territories: a systematic analysis for the Global Burden of Disease Study 2021.BMJ Glob Health. 2025;10(3):e017198.
- Kugaudaite G, et al. Menstrual blood-derived mesenchymal stromal cell extracellular vesicles stimulate chondrocytes and cartilage extracellular matrix synthesis in vitro. Sci Rep. 2026;16:11059.
- Naji A et al. Biological functions of mesenchymal stem cells and clinical implications.Cell Mol Life Sci. 2019;76(17):3323-3348.
- Zhang T, et al. The tiny giants of regeneration: MSC-derived extracellular vesicles as next-generation therapeutics.Front Cell Dev Biol. 2025;13:1612589.
- Sophia Fox AJ, et al. The basic science of articular cartilage: structure, composition, and function.Sports Health. 2009;1(6):461-468.
