Three Types of Stem Cell Therapy, Explained
Learn the differences between autologous, allogeneic, and culture-expanded stem cells, how each works, and why product quality can vary.
When patients research “stem cell therapy,” they often discover that the same phrase is used to describe several distinct therapies. Understanding these differences is important.
Stem cell therapies used in orthopedic and regenerative medicine generally fall into three categories:
1. Autologous stem cells, which use a patient’s own cells
2. Allogeneic stem cells, which use donor-derived cells
3. Culture-expanded stem cells, which can use both autologous and allogeneic stem cells that are grown in a laboratory to achieve higher, standardized cell doses
Although these approaches are often grouped together under the umbrella of “stem cell therapy,” they differ significantly in how they are sourced and what they contain.
1. Autologous Stem Cells: Using a Patient’s Own Cells
Autologous stem cells come from your own body. In orthopedic medicine, they are most commonly obtained from:
- Bone marrow
- Adipose tissue (fat)
Bone Marrow Aspirate Concentrate and Microfragmented Adipose Tissue
| How it is Made | Contains | |
|---|---|---|
| Bone Marrow Aspirate Concentrate (BMAC) | Collecting bone marrow, typically from the pelvisProcessing it at the point of care to concentrate the biologic components1Injecting the concentrate into the joint, tendon, ligament, or other structure using image guidance | A mixture of cells and biologic signaling molecules, including mesenchymal stem cells (also referred to as mesenchymal stromal cells or MSCs), along with growth factors, cytokines, IL-1ra, and other biologic components |
| Microfragmented Adipose Tissue (MFAT) | Collecting a small amount of a patient’s own fat tissue and mechanically processing it without enzymatic digestion. | Naturally contains mesenchymal stem cells within its supportive tissue structureIt preserves many of the tissue’s natural structural components, including:Extracellular matrixBlood vesselsSupportive connective tissueBiologically active signaling moleculesAdipose tissue is a rich source of these cells, and reported concentrations vary between studies and measurement methods |
Patients often confuse PRP (platelet-rich plasma) with stem cell therapy because both are autologous biologic therapies. However, PRP is created by concentrating platelets from the patient’s blood and does not contain mesenchymal stem cells. Instead, it delivers a high concentration of growth factors that may support healing and provide anti-inflammatory effects.4
2. Allogeneic Stem Cells: Donor-Derived Tissue
Allogeneic stem cells come from donated human tissue rather than from the patient themselves.
Common donor sources include:
- Wharton’s jelly (the connective tissue within the umbilical cord)
- Umbilical cord blood
- Amniotic tissue and fluid
- Donor bone marrow
- Donor adipose tissue
What Allogeneic Products Contain
Allogeneic products differ from one another in what they contain, and each type has its own biologic profile.
Wharton’s jelly and amniotic tissue products commonly contain:
- Growth factors
- Cytokines
- Extracellular matrix
- Collagen
- Hyaluronic acid
- Exosomes and other extracellular vesicles
Stem cell content may vary between these products. Where viable cell counts are lower or even absent, the growth factors, cytokines, extracellular matrix, and extracellular vesicles they contain remain biologically active and are the subject of ongoing research.
3. Culture-expanded Stem Cells: Higher, Standardized Cell Counts
The third category is culture-expanded stem cells.
Rather than being used immediately after collection, these cells are grown under carefully controlled laboratory conditions until they reach much higher and more standardized cell numbers.
Compared with conventional autologous or donor-derived products, culture expansion offers:
- Higher cell counts
- More standardized dosing
- Greater consistency between production batches
Why Higher Cell Counts May Matter
Cell dose is an active research question. Does administering a higher dose of stem cells provide a different effect? What effects, if any, are provided? When stem cells are delivered through the bloodstream, many are naturally retained in the lungs before reaching other tissues. This phenomenon is known as the pulmonary first-pass effect. Clinical research is trying to understand if providing a higher cell count can overcome this effect and whether this is clinically relevant.2
| Availability in the United States |
|---|
| Culture expansion reached an important milestone recently.In December 2024, the U.S. Food and Drug Administration approved Ryoncil (remestemcel-L-rknd), the first FDA-approved mesenchymal stromal cell product, manufactured through culture expansion. Its approval is for pediatric steroid-refractory acute graft-versus-host disease. Further indications are the focus of ongoing clinical trials.3 |
Final Thoughts on Stem Cell Therapies
The phrase “stem cell therapy” describes a broad category of therapies rather than a single type.
Autologous stem cells, allogeneic stem cells, and culture-expanded stem cells each represent distinct categories with different sources, biologic characteristics, and levels of clinical availability. Each category has unique properties that researchers continue to study for their potential applications with various injuries.
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. You can learn more about his practice here: https://www.steveyoonmd.com/contact/
Frequently Asked Questions
What is the difference between autologous and allogeneic stem cells?
Autologous stem cells come from a patient’s own body, most commonly through bone marrow concentrate or microfragmented adipose tissue. Allogeneic stem cells come from donated tissue, such as umbilical cord, amniotic tissue, bone marrow, or adipose tissue.
What do umbilical cord and Wharton’s jelly products contain?
These products contain a mix of biologically active components, including growth factors, cytokines, extracellular matrix, collagen, hyaluronic acid, exosomes, and other extracellular vesicles.5 Viable stem cell content varies between products, and the other components found in these products are biologically active in their own right.
What are culture-expanded stem cells?
Culture-expanded stem cells are cells that have been grown in a laboratory to achieve higher, standardized cell numbers. Cell quality and viability can also be monitored.
References
1. Gaul F, Bugbee WD, Hoenecke HR Jr, D’Lima DD. A Review of Commercially Available Point-of-Care Devices to Concentrate Bone Marrow for the Treatment of Osteoarthritis and Focal Cartilage Lesions. Cartilage. 2019;10(4):387-394.
2. Fischer UM, Harting MT, Jimenez F, et al. Pulmonary passage is a major obstacle for intravenous stem cell delivery. Stem Cells and Development. 2009;18(5):683-692.
3. U.S. Food and Drug Administration. FDA approval of Ryoncil for steroid-refractory acute graft-versus-host disease in pediatric patients, December 18, 2024.
4. Sundman EA, Cole BJ, Karas V, Della Valle C, Tetreault MW, Mohammed HO, Fortier LA. “The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis.” American Journal of Sports Medicine. 2014 Jan;42(1):35-41.
5. Gupta A, El-Amin SF, Levy HJ, Sze-Tu R, Ibim SE, Maffulli N. “Umbilical cord-derived Wharton’s jelly for regenerative medicine applications.” Journal of Orthopaedic Surgery and Research. 2020;15(1):49. PMID: 32054483
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