Autologous versus allogeneic stem cells — what's the difference? Lessons from the POSEIDON heart study and Yamaguchi University's cirrhosis research

Summary — In stem cell information, 'autologous' (自家) means using the patient's own cells and 'allogeneic' (他家) means using cells from another person (a donor). The POSEIDON study (2012), by the University of Miami and others, compared autologous and allogeneic mesenchymal stem cells directly in heart patients and reported that both reduced scar size without worrying safety problems. Japan's Yamaguchi University started with autologous bone marrow cell infusion in cirrhosis (2006) and has broadened its research to cultured and donor cells. This article sets out the pros and cons of each approach.

Autologous cells: using the patient's own cells

Autologous cells are collected from the patient's own bone marrow, fat or blood and given back as they are or after culture. The main advantage is little concern about immune rejection. There are limits, however. First, procedures such as bone marrow collection or liposuction place a burden on the patient. Second, culture takes several weeks, which can make timely administration difficult in acute conditions. Third, in older patients or those with chronic disease, cell number and function may be reduced, so cell quality can vary from patient to patient.

Allogeneic cells: using donor cells

Allogeneic cells are obtained from the bone marrow, fat or umbilical cord of healthy young donors, expanded in large quantities and quality-controlled before use in many patients. They can be prepared and stored in advance for immediate use, and consistent quality is easier to maintain. Mesenchymal stem cells carry few of the surface molecules that trigger immune responses, so donor cells are known to be relatively well accepted, though immune responses with repeated dosing must continue to be evaluated. The mesenchymal stem cell product approved in Japan in 2015 for acute graft-versus-host disease is also an allogeneic product.

A direct comparison: POSEIDON (2012)

POSEIDON randomised 30 patients with ischaemic cardiomyopathy — reduced heart function after a heart attack — to autologous or allogeneic bone marrow-derived mesenchymal stem cells injected by catheter into the inner heart wall, also comparing three doses. Over one year, no worrying immune reactions or serious arrhythmias were reported with either approach, and scar size measured by CT decreased. Six-minute walk distance and quality-of-life scores improved in some groups, but left ventricular ejection fraction, a key measure of heart function, did not change significantly. The study is often cited as safety evidence for using allogeneic cells in the heart, and it led to the allogeneic DREAM-HF study of more than 500 patients (2023), which did not meet its primary outcome but reported some secondary outcome results.

A Japanese example: Yamaguchi University's cirrhosis research

A Yamaguchi University team developed 'autologous bone marrow cell infusion therapy', collecting bone marrow from nine patients with cirrhosis, separating mononuclear cells and infusing them intravenously the same day, and reported in Stem Cells in 2006 improved serum albumin and Child-Pugh scores after infusion. However, the method required collecting a large volume of bone marrow under general anaesthesia, a heavy burden for cirrhosis patients with impaired clotting. The team has since broadened its research to culturing mesenchymal stem cells from a small amount of bone marrow and to using donor cells — a clear illustration of moving towards allogeneic approaches to reduce the limits of autologous ones. For reference, the UK randomised phase 2 REALISTIC study (2018) did not find improved liver function scores with a different autologous stem cell approach.

In short

Autologous cells carry little rejection concern but involve collection burden and individual variation in quality; allogeneic cells are easier to use immediately and to quality-control but require ongoing evaluation of immune responses. When reading information, check which cells were used and what kind of study tested that approach. See the 'Heart Failure' and 'Liver Cirrhosis' pages for details.

Frequently asked questions

Q. Which is more effective, autologous or allogeneic?
In POSEIDON, scar size decreased with both approaches, and no clear conclusion was reached that one was more effective. The suitable approach may differ with the condition, route of administration and the patient's age and health.

Q. Do allogeneic cells require immunosuppressants?
Mesenchymal stem cells provoke little immune response, so in many studies, including POSEIDON, they were given without immunosuppressants. By contrast, studies transplanting neurons or islet cells made from iPS cells often use immunosuppressants, so it depends on the cell type.

Q. Are allogeneic cell products approved in Japan?
An allogeneic mesenchymal stem cell product for acute graft-versus-host disease (2015) and an allogeneic adipose-derived mesenchymal stem cell product for complex perianal fistulas in Crohn's disease (2021) have been approved. No mesenchymal stem cell product has yet been approved for heart or liver disease.

How to look up clinical trial information

Ongoing and completed clinical trials can be checked on public registries. ClinicalTrials.gov, run by the U.S. National Library of Medicine, and jRCT, run by Japan's Ministry of Health, Labour and Welfare, publish each study's purpose, eligibility criteria, intervention, outcomes, institutions and status. Results are later published as journal papers, and the reference links below this article lead to the original information. It is also worth knowing that interventions not publicly registered are difficult to verify from outside, in both design and results.

The above summarises results reported in published papers. University and institute names are given to identify research sources, not to introduce or recommend any medical institution. The suitability of any treatment is decided by the medical team.

Heart, Liver & Diabetes →