The Evolution from Autologous to Allogeneic Cell Therapies
Autologous vs. Allogeneic: What’s the difference?
Stem cell therapies can be differentiated by the source of donor stem cells in relation to the recipient. Autologous stem cells are harvested from the patient that receives the cells. Allogeneic stem cells are harvested from a healthy donor of the same species. Xenogeneic stem cells are harvested from a healthy donor of a different species. Although all types have advantages and disadvantages, recent studies in humans indicate that allogeneic off-the-shelf mesenchymal stem cell (MSC) therapy often outperforms autologous MSC therapy.1 Several factors that influence the advantages of allogeneic MSC therapy are outlined below.
Age
Multiple studies have demonstrated that aging and various disease states adversely affect MSC functionality.1,2 Stem cells from older patients have reduced proliferation, decreased osteogenic and chondrogenic potential (meaning they are less able to form new bone and cartilage cells), increased senescence (more likely to be in a state of permanent growth arrest), and decreased migrating ability compared to stem cells harvested from younger patients.1 Because stem cells are often needed most in conditions associated with increased age (i.e. arthritis, chronic kidney disease), autologous cells from an older animal may be less effective.1
Illness
Stem cells harvested from non-healthy individuals exhibit reduced potency compared to healthy donors. Studies using autologous MSC in humans with inflammatory diseases have shown have showed impaired immunomodulatory effects compared to healthy donors.1
Dose
Utilizing allogenic stem cells allows for administration of a known target dose. Individual patient variability and differences in harvesting, culturing, and processing techniques can greatly affect stem cell number and quality, limiting the ability to acquire the desired dose in animals receiving autologous stem cell therapy.
Efficacy
Clinical studies that directly compare autologous and allogenic MSCs are limited. Available results indicate that both have similar outcomes and in some cases allogenic therapy is more effective.1
Accessibility
One of the biggest advantages to allogenic stem cell therapy is they provide an immediate, “off-the-shelf” source of stem cells from a healthy donor at a specified dose that can be thawed and administered as needed. Stem cells harvested in a good manufacturing practice (GMP) compliant lab as regulated by the FDA help ensure consistent stem cell quality. Stem cells are stable for 18+ months after storage and remain stable when shipped under appropriate freezing conditions.
Urgency
The process for autologous stem cell harvest and culture often takes weeks, whereas allogenic stem cells can be available within 24 hours. This is highly advantageous in patients with inflammatory conditions that may need urgent treatment.
Immunogenicity/stem cell rejection
Although there is potential for generation of alloreactive antibodies and immune rejection with allogeneic stem cell administration, that risk is thought to be low.1 MCSs are considered “immune-evasive” or “immune-privileged” as they express low levels of MHC class I and lack MHC class II expression, allowing them to avoid the innate and adaptive immune responses. Stem cells are expected to survive for a short period of time in the body. When administered intravenously, the majority get trapped in the lungs and they exert more of a “hit and run” effect by influencing the body’s own cells. Their short lifespan makes a delayed or long-term immune reaction unlikely.
1. Durand N, Zubair AC. Autologous versus allogeneic mesenchymal stem cell therapy: The pros and cons. Surgery. 2022;171(5):1440-1442. doi:10.1016/j.surg.2021.10.057
2. Taguchi T, Borjesson DL, Osmond C, Griffon DJ. Influence of Donor’s Age on Immunomodulatory Properties of Canine Adipose Tissue-Derived Mesenchymal Stem Cells. Stem Cells Dev. 2019;28(23):1562-1571. doi:10.1089/scd.2019.0118
