Mesenchymal Stem Cells: What They Are, Where They Come From, and How They Work

What Are Mesenchymal Stem Cells?

Mesenchymal stem cells (MSCs) are a type of cell found in the adult human body. They have the ability to self-renew and differentiate into specialized cell types, including bone, cartilage, and fat cells [1]. MSCs also release signaling molecules that help regulate inflammation and promote tissue repair [2].

• Embryonic stem cells are pluripotent, meaning they can develop into almost any type of cell in the body [3, 4].
• Adult stem cells can be divided into two categories:

When and How Were MSCs Discovered?

The discovery of mesenchymal stem cells is closely linked to the work of Alexander Friedenstein and his colleagues in the 1960s and 1970s [6]. The researchers transplanted bone marrow into other parts of the body and observed that both bone tissue and bone marrow formed at the transplantation sites [6]. This suggested that bone marrow contained not only blood-forming cells but also cells capable of producing bone tissue.

To identify these cells, Friedenstein’s team grew them in the laboratory in 1970. They discovered that the cells formed distinct colonies, each originating from a single cell [6].

This discovery led to their first name: Friedenstein and fellow researcher Maureen Owen called them bone marrow stromal stem cells [6]. The term mesenchymal stem cells was introduced later, in 1991, by Arnold Caplan and became widely adopted in scientific literature [6].

In 2004, another important milestone followed: MSCs were successfully used in a clinical setting to treat severe graft-versus-host disease (GVHD), a serious complication of transplantation [2].

Where Do Mesenchymal Stem Cells Come From?

Sources of MSCs (adipose tissue, bone marrow, placenta, umbilical cord, and dental pulp) and their mechanisms of action in immune-mediated and inflammatory diseases. Source: Han X. et al., Signal Transduction and Targeted Therapy, 2025 [5]. Licensed under CC BY 4.0.

Bone Marrow

Bone marrow is the most extensively studied source of MSCs [7]. However, these cells are relatively rare, accounting for only about 1 in every 10,000–100,000 bone marrow cells [1]. Therefore, MSCs must first be expanded in the laboratory to obtain sufficient numbers for therapeutic use [7].

Adipose Tissue

MSCs derived from adipose tissue are obtained from lipoaspirate collected during liposuction or through an abdominal fat biopsy [8]. Adipose tissue contains a relatively high number of MSCs, and harvesting them is less invasive than collecting bone marrow [8].

Umbilical Cord Blood and Tissue

MSCs can be isolated from both umbilical cord blood and umbilical cord tissue [7]. Umbilical cord blood-derived MSCs retain their ability to proliferate for longer than MSCs from adult tissues, but have a limited capacity to differentiate into fat cells [7].

Other Sources: Dental Pulp, Placenta, and Synovial Tissue

MSCs can also be isolated from dental pulp, the placenta, and synovial tissue within joints [5, 9]. In comparative studies, synovial tissue-derived MSCs demonstrated the greatest capacity to form cartilage tissue [9].

How MSCs Work: Key Properties

Ability to Differentiate into Other Cell Types

Differentiation is the process by which a cell develops into a more specialized cell type. Under laboratory conditions, MSCs can differentiate into osteoblasts (bone-forming cells), chondrocytes (cartilage cells), and adipocytes (fat cells) [1].

Immunomodulatory and Anti-inflammatory Properties

MSCs help regulate the immune system and reduce excessive inflammation. They promote the development of regulatory T cells, which help prevent an excessive immune response, and encourage macrophages to adopt an anti-inflammatory state [2, 7].

Paracrine Effects: Release of Growth Factors and Cytokines

MSCs produce many of their effects by releasing biologically active molecules into their surrounding environment. This process is known as paracrine signaling [2, 7].

These molecules include growth factors, cytokines, and exosomes (small extracellular vesicles that carry signals between cells) [2].

Learn more about exosomes in our article: Exosome Therapy (link to article).

Autologous vs. Allogeneic MSCs: What’s the Difference?

Autologous MSCs are obtained from the patient’s own body, while allogeneic MSCs come from a healthy donor [2]. The physician determines which type to use based on the patient’s health, laboratory test results, and treatment needs.

• Autologous MSCs (the patient’s own cells) require tissue collection and time for laboratory expansion. Their properties may vary depending on the patient’s age and overall health.

• Allogeneic MSCs (donor-derived cells) are collected and prepared in advance and undergo testing before clinical use.

Medical Applications of MSCs

Mesenchymal stem cells (MSCs) are being investigated for potential applications across a wide range of medical specialties.

Joint and Musculoskeletal Disorders

MSCs are being studied for their potential to support cartilage repair and treat osteoarthritis [1].

Learn more: Cell Therapy for Joint Disorders (link to article).

Neurological Disorders

In patients with ischemic stroke, MSC administration has been associated with reduced neurological impairment without an increase in adverse events [10].

Learn more: Neurology (link to category).

Endocrine Disorders

In patients with type 2 diabetes, MSC therapy has been associated with improved blood glucose control. A meta-analysis of nine clinical studies found a reduction in glycated hemoglobin (HbA1c) levels following treatment [11].

These findings suggest that MSCs may have potential as an additional treatment alongside standard diabetes care.

Learn more: Endocrinology (link to category).

Vascular Surgery

MSCs are being investigated for their potential to promote the formation of new blood vessels in patients with critical limb ischemia [1].

Learn more: Vascular Surgery (link to category).

Supporting Healthy Aging and Physical Function

MSCs are being studied for their potential to help people with age-related frailty, a condition characterized by declining physical strength and endurance.

In studies involving older adults, donor-derived MSC therapy showed a favorable safety profile and demonstrated potential to improve walking endurance and reduce inflammatory markers in the blood [12].

Regenerative Dermatology and Aesthetic Medicine

In addition to MSCs, other cell-based technologies are used in this field, including dermal fibroblasts (link to article) and exosomes for alopecia (link to article).

Safety of MSC Therapy: What Research Shows

Clinical studies suggest that mesenchymal stem cell (MSC) therapy has a generally favorable safety profile. The most commonly reported side effect is a temporary fever. Less common adverse effects include injection-site reactions, fatigue, constipation, and sleep disturbances [13, 14].

Evidence from Clinical Studies

• The 2012 SafeCell meta-analysis found no significant association between MSC administration and cancer, infections, organ-related complications, or mortality [13].

• An updated meta-analysis published in 2020 supported these findings, drawing on a larger body of clinical evidence [14].

• One of the most extensively studied applications of MSC therapy is severe graft-versus-host disease (GVHD), a complication of bone marrow transplantation in which donor immune cells attack the recipient’s tissues [7]. In patients who do not respond to steroid treatment, MSC therapy has been associated with response rates of 48–71% [2]. In 2024, the U.S. Food and Drug Administration (FDA) approved the first MSC-based therapy for this condition in children aged 2 months and older [15].