As regenerative medicine becomes more mainstream, so too does the language surrounding how therapies are sourced, prepared, and applied. Among the most frequently misunderstood terms is “culture and expanded.” Whether you’re a clinician considering advanced therapies for your patients or a scientist evaluating your product pipeline, understanding this concept is essential—not just for scientific integrity, but also for regulatory compliance and ethical transparency.
In this article, we’ll break down what “culture and expanded” means, why it matters, and how it shapes the landscape of biologics and regenerative interventions.
What Does "Culture and Expanded" Mean?
“Culture and expanded” refers to the process of isolating cells from a donor tissue source and growing them in vitro (outside the body) to increase the number of cells before therapeutic use. This is most commonly done with mesenchymal stem/stromal cells (MSCs), epithelial cells, or other regenerative cell types to achieve a therapeutic dose that would not be possible through direct extraction alone [1].
The goal is to multiply the cellular population, often while selecting for specific traits such as surface markers or growth factors, before clinical use.
The Regulatory Implications
While the science of cell expansion may be elegant, the regulatory perspective is decidedly more cautious. The U.S. Food and Drug Administration (FDA) classifies cell culture and expansion as more than minimal manipulation—a key distinction under 21 CFR Part 1271 [2].
To qualify for regulation solely under Section 361 of the Public Health Service (PHS) Act, a product must meet specific criteria, including minimal manipulation. Culturing and expanding cells exceeds that threshold because it alters the biological characteristics of the cells, particularly their proliferative potential, gene expression, and phenotype [3].
Products that are culture-expanded generally fall under Section 351, which means:
- They are considered biological drugs.
- They require an Investigational New Drug (IND) application and Biologics License Application (BLA) before they can be marketed.
- They must meet extensive safety, purity, potency, and efficacy standards.
Why Expansion Alters Cell Behavior
Cells grown in vitro experience selective pressures not present in vivo. These include:
- Replicative senescence: After multiple doublings, many cells lose potency and regenerative capacity [4].
- Phenotypic drift: Expanded cells can begin expressing different genes than their original in vivo counterparts [5].
- Genomic instability: Extended culture can lead to chromosomal abnormalities, increasing the risk of adverse outcomes [6].
Thus, even if expanded cells originate from a safe, healthy donor, the end product can differ significantly from the original tissue—clinically and molecularly.
The Market Confusion
In the commercial space, terms like “stem cell therapy,” “expanded MSCs,” and “minimally manipulated” are sometimes used inconsistently or inaccurately. Some clinics may use expanded cells without proper regulatory approvals, claiming exemptions or disguising procedures under less regulated categories [7].
This creates a compliance risk for providers and a safety risk for patients, who may be unaware that they are receiving an unapproved biologic drug.
Nova Vita Labs' Position on Expansion
At Nova Vita Labs, we prioritize scientific integrity and regulatory compliance. Our amniotic fluid-derived products are acellular and not culture-expanded, ensuring they remain within the scope of minimally manipulated designations. We believe in transparency regarding processing methods and in educating both providers and patients on what that means.
Conclusion: Expansion Doesn’t Always Mean Better
While culturing and expanding cells may offer therapeutic scalability, it also brings complexity. Understanding whether a product is culture-expanded is crucial for evaluating:
- Regulatory pathway
- Risk profile
- Clinical validity
As regenerative therapies evolve, so too must our standards for clarity, rigor, and compliance.
For healthcare providers, scientists, and patients alike, asking the right questions about how products are processed is more important than ever. Expansion may boost quantity—but quality, safety, and ethical use must always lead.
References
- Samsonraj, R. M., et al. "Establishing criteria for human mesenchymal stem cell potency." Stem cells 33.6 (2015): 1878–1891.
- U.S. Food and Drug Administration. “21 CFR Part 1271 – Human Cells, Tissues, and Cellular and Tissue-Based Products.” https://www.ecfr.gov/current/title-21/chapter-I/subchapter-L/part-1271
- Galipeau, Jacques, and Arnold I. Caplan. "The mesenchymal stromal cells dilemma—does a negative phase III trial of random donor MSCs mean that autologous cells are better?" Cytotherapy 18.1 (2016): 5–7.
- Wagner, Wolfgang, et al. "Replicative senescence of mesenchymal stem cells: a continuous and organized process." PLoS One 3.5 (2008): e2213.
- Schellenberg, Annette, et al. "Population dynamics of mesenchymal stromal cells during culture expansion." Cytotherapy 14.4 (2012): 401–411.
- Tarte, K., et al. "Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation." Blood 115.8 (2010): 1549–1553.
- Turner, Leigh. "The U.S. stem cell market and the FDA: A time for action." Cytotherapy 17.12 (2015): 1663–1667.
