Following the box-office success of the film Spider-Man: Brand New Day, public attention has once again turned to Lizard, the series' iconic villain who possesses a fictional ability to regenerate entire limbs. While movie-style regeneration remains purely in the realm of science fiction, a practical question often arises in real-world medicine: Does culturing and administering a higher volume of stem cells translate into stronger regenerative effects?
Healthcare provider 365mc recently addressed this question in a newly released report, laying out key considerations for when stem cells are cultured outside the body or administered in multiple doses.
In the Spider-Man storyline, scientist Dr. Curt Connors attempts to apply reptilian regenerative traits to humans to restore his lost arm, an experiment that backfires and turns him into Lizard. Real-world regenerative medicine operates under vastly different principles. In clinical settings, researchers investigate whether mesenchymal stem cells—sourced from adipose tissue or bone marrow—can help repair damaged human tissue.
Understanding Cell Count vs. Biological Function
While mesenchymal stem cells can be cultured in vitro to increase their numbers, 365mc emphasized that a higher cell count alone does not guarantee a proportional rise in therapeutic effectiveness.
"It is overly simplistic to assume that increasing cell numbers through culturing directly boosts treatment efficacy," said Kim Jung-eun, director of the 365mc Adipose Stem Cell Center. "One must carefully evaluate multiple variables, including the culture medium, culture duration, passage number, and cryogenic storage methods."
As supporting evidence, 365mc cited a 2020 review by researchers at Sapienza University of Rome examining adipose-derived stem cells. The authors noted that as "passage culturing"—repeatedly transferring cultured cells into new growth vessels—continues, the cells gradually differentiate and lose some of their immune-suppressing capabilities. The study further indicated that the immunomodulatory functions of stem cells vary depending on their culture environment.
However, because the paper was a literature review synthesizing prior studies rather than a direct clinical trial in human patients, it does not, by itself, establish that extensive culturing reduces real-world treatment effectiveness in humans.
Immune Responses in Repeat Administration
To illustrate the potential risks of repeated administration, 365mc highlighted a 2017 study conducted by Texas A&M University. Researchers divided 18 horses into three groups and injected bone marrow-derived mesenchymal stem cells into their joints twice at four-week intervals.
The test groups were structured as follows: one receiving self-derived (autologous) cells cultured with autologous serum during the final 48 hours to reduce bovine protein contamination; a second group receiving donor-derived (allogeneic) cells processed under the same conditions; and a third group receiving autologous cells cultured with standard fetal bovine serum (FBS) without the contamination-reduction process.
FBS is widely used in culture media to supply essential growth factors, but residual bovine proteins left on the cultured cells can trigger immune reactions upon re-injection.
While no significant differences appeared after the first injection, the second injection produced distinct reactions. Horses receiving donor cells and those receiving autologous cells cultured with FBS exhibited elevated counts of nucleated inflammatory cells in their synovial fluid. The group receiving FBS-cultured autologous cells also displayed heightened pain indicators.
The researchers concluded that the equine immune system recognized foreign antigens upon repeat exposure—either from donor cells or residual bovine proteins from the culture medium. However, as an animal study involving joint injections in horses, these results cannot be directly extrapolated to human autologous adipose-derived stem cell treatments.
A 2021 follow-up study by the same Texas A&M team further demonstrated how culture methods influence outcomes. Working again with 18 horses, researchers cultured autologous bone marrow mesenchymal stem cells using three different media: individual horse bone marrow supernatant, pooled bone marrow supernatant, or FBS.
Upon administering a second joint injection alongside lipopolysaccharide (LPS) to induce joint inflammation, the FBS group experienced significantly greater joint swelling and increased synovial fluid volume. In vitro assays confirmed that antibodies targeting bovine proteins attacked the FBS-cultured cells, causing cell death. Still, because LPS was co-injected to create an artificial inflammatory state, the study does not directly prove that FBS-cultured autologous cells cause inflammation in human patients under normal conditions.
"These findings highlight why researchers must evaluate not only the origin of the stem cells, but also the specific conditions under which they were cultured," noted Kim Jin-ok, head of research at Monitcell.
Safety, Efficacy, and Regulatory Frameworks
365mc also noted the advantages of uncultured autologous cells, such as stromal vascular fraction (SVF) isolated from a patient's own fat tissue. SVF avoids immune mismatch risks and bypasses potential cellular alterations caused by prolonged culturing. However, SVF is not a pure stem cell isolate; according to South Korea's Ministry of Food and Drug Safety, it is a complex mixture containing adipose-derived stem cells alongside fibroblasts, immune cells, microvascular endothelial cells, and adipose precursor cells.
Even uncultured autologous cells do not automatically guarantee safety or therapeutic success, as outcomes depend heavily on cell isolation methods, administration sites, and specific medical conditions.
In South Korea, cultured stem cell treatments cannot be administered at medical discretion as routine care. Providers must use approved advanced biopharmaceuticals or follow legally prescribed procedures, such as clinical trials or authorized advanced regenerative medicine research plans.
Under the advanced regenerative medicine treatment system introduced by the Ministry of Health and Welfare in February 2025, designated institutions must obtain committee approval for specific treatment plans prior to administration. For medium- and high-risk procedures, institutions must first complete preliminary clinical research of equivalent scope and purpose.
"Patients considering stem cell therapy should verify whether the procedure complies with authorized domestic regulations, understand what specific cell types are being used, and ensure there is sufficient evidence regarding repeat administration safety," said Director Kim Jung-eun. "Decisions should always be made after thorough consultation with a medical specialist."
