What is Cell Therapy?
Cell therapies encompass a wide range of therapeutic products that use living cells to repair or restore biological function. Among these are non-genetically modified cell therapies, which rely on the intrinsic properties of cells rather than genetic alteration. This group includes minimally manipulated cell therapies, which are cells or tissues that have undergone limited processing for the purpose of reconstruction, repair, or replacement in the recipient as in the donor—a concept known as homologous use. In contrast, products subjected to more extensive processing that changes their biological activity, differentiation potential, or metabolic function are regulated as biological products, requiring full clinical evaluation and approval under biologic drug regulations. A distinct subset of these are genetically modified cell therapies that involve the deliberate introduction of genetic material, such as with CAR-T therapy, and will be discussed separately as cell-based gene therapies.
In this guide, learn how CDMOs and therapeutic firms can evaluate their needs and select the raw and cellular starting materials that will set their programs up for success.
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Current cell therapy development programs target a broad range of diseases. In oncology, investigational therapies address malignancies such as acute myelogenous leukemia, liver cancer, and ovarian cancer, while non-oncology therapies focus on conditions including graft-versus-host disease, osteoarthritis, diabetes, acute respiratory distress syndrome, and Parkinson’s disease. Non-genetically modified cell therapies span multiple cell types, including stem and progenitor cells, immune cells, and other differentiated cell populations. Cell therapy types that have had the greatest clinical success are highlighted below:
Cell Therapy Workflow
The manufacturing of cell therapies involves a series of tightly controlled steps designed to ensure product quality, safety, and therapeutic efficacy. This workflow broadly outlines the stages of non-genetically modified cell therapies—from patient or donor cell collection through processing, formulation, and preparation for clinical administration—that collectively define the path from raw cell material to therapeutic product.
Reagent preparation: Reagents used in the cell therapy manufacturing process must be formulated and controlled in accordance with strict regulatory and quality guidelines. These include cell isolation reagents, culture media, supplements, growth factors, and other product- or process-specific materials essential for cell expansion, differentiation, and preservation.
Cell collection: Cells are obtained from donor blood, tissue, or established cell cultures and then processed to ensure purity and viability. They are typically washed to remove residual impurities and to optimize the cellular microenvironment. Specific cell populations are subsequently isolated or enriched based on defined phenotypic or functional markers to meet product specifications and therapeutic requirements.
Treatment and expansion: Cells may undergo specific treatments tailored to the intended pharmacological mechanism of the therapy. These manipulations can involve inducing functional changes such as cellular activation, reprogramming of cell identity, or stimulation of controlled proliferation. The selected cell population is then expanded in vitro under defined culture conditions to achieve the required quantity for clinical use.
Formulation and storage: Cells are formulated into defined doses to ensure clinical efficacy, safety, and consistency. Formulation parameters, such as cell concentration, phenotype, and delivery medium, are carefully controlled, and dosing may be individualized based on patient-specific factors or therapeutic indication. Generally, they will undergo cryopreservation to maintain stability during storage and transport, with strict control of temperature and handling conditions.
Quality control and testing: Comprehensive quality control and testing are implemented throughout the cell therapy manufacturing process to ensure product safety, identity, purity, and potency. Safety testing includes screening for viral and microbial contamination as well as adventitious agents that could compromise product integrity. Genomic stability assessments may also be performed to detect any chromosomal abnormalities or mutations that could increase the risk of tumorigenicity or other adverse effects.
Administration: Therapeutic cells are administered to the patient through a specified route (e.g., intravenous infusion, local injection, or surgical implantation). In some therapies, particularly hematopoietic stem cell or immune cell treatments, patients may undergo conditioning regimens such as chemotherapy or immunosuppression to facilitate engraftment, reduce immune rejection, or create space within target tissues. Following treatment, patients will also be monitored for efficacy, side effects, and long-term outcomes.
Autologous vs. Allogeneic Cell Therapy
In the development of cell-based therapies, one of the most fundamental distinctions is whether the source material is autologous or allogeneic. Each approach carries unique scientific, logistical, and regulatory considerations that shape research strategy and product development.
Autologous cell therapy uses cells collected directly from the patient, modified, then re-introduced to the same patient for treatment. Because the cells are genetically matched to the recipient, the risk of immune rejection is generally lower than from material derived from other donors. This method is dependent on the needs of each patient and the individualized manufacturing process for each patient adds complexity to production scale-up, cost control, and quality standardization.
Allogeneic cell therapy relies on donor material sourced from individuals other than the patient. This approach enables more standardized and scalable manufacturing, since a single donor’s cells can be expanded to create multiple doses for many patients. However, the use of non-self cells introduces the risk of immune rejection, which must be managed through careful product design and clinical strategy.
The choice between autologous and allogeneic strategies impacts every stage of cell therapy product development, from donor selection and cell sourcing to manufacturing workflows, safety testing, and regulatory submissions. Autologous approaches tend to emphasize individualized protocols and patient-specific logistics. Meanwhile, allogeneic cell therapy manufacturers must confirm donor eligibility through rigorous screening and testing procedures. Screening involves a detailed review of medical history and risk factors for communicable diseases, as well as potential exposures such as xenotransplantation. Testing, typically performed on donor blood specimens, must use approved, or cleared kits in certified laboratories to ensure reliability and compliance.
Cell Therapy Types
Mesenchymal stromal cells
Mesenchymal stromal cells (MSCs) are self-renewing, multipotent progenitors capable of differentiating into mesodermal lineages such as bone, cartilage, and muscle. Their low immunogenicity and inherent immunomodulatory properties make them promising candidates for off-the-shelf cellular therapies. MSC-based therapies are derived from both autologous and allogeneic sources, most commonly from bone marrow, adipose tissue, and umbilical cord. Bone marrow-derived MSCs are among the most frequently used in clinical research, while neonatal tissue-derived MSCs often show enhanced proliferative capacity, longer lifespan, and greater differentiation potential. MSC-based cell therapies in development target a variety of diseases, including osteoarthritis, bone loss, heart failure, graft-versus-host disease, Crohn’s disease, amyotrophic lateral sclerosis, and sexual dysfunction. Currently, there is one U.S. FDA approved MSC cell therapy, Ryoncil, which works to inhibit T cell activation.
Barriers to clinical success of MSC-based cell therapies include poor cell survival, suboptimal engraftment, and inefficient homing to target tissues. Donor variability and heterogeneity among tissue sources can also complicate consistency and reproducibility. These limitations have motivated efforts to develop strategies for enhancing MSC performance utilizing both genetic and non-genetic modification strategies. Examples include preconditioning (“priming”) cells or introducing genes that improve survival and immunomodulation.
Hematopoietic stem cells
Hematopoietic stem cells (HSCs) possess the unique capacity to self-renew and differentiate into all blood and immune cell lineages, forming the foundation of the hematolymphoid system. They play a critical role in sustaining hematopoiesis throughout life and enabling recovery from physiological or pathological stress. Harnessing these regenerative properties, hematopoietic stem cell transplantation (HSCT) has become a cornerstone therapy for reestablishing functional hematopoiesis in patients with hematologic malignancies, immune deficiencies, and certain metabolic disorders.
Most FDA-approved hematopoietic stem cell (HSC) therapies rely on allogeneic hematopoietic progenitor cells (HPCs), as well as monocytes, lymphocytes, and granulocytes derived from human umbilical cord blood. Approved products in this category include Allocord, Clevecord, Ducord, Hemacord, Regenecord, and others. These therapies function by enabling transplanted progenitor cells to migrate to the bone marrow, where they proliferate and mature into the full spectrum of hematopoietic and immune cell lineages. The mature cells then repopulate the bloodstream and tissues, helping to restore normal blood counts and immune function in patients with bone marrow failure or after myeloablative treatment. Another example is Omisirge (omidubicel-onlv), an allogeneic cord blood–derived therapy that introduces nicotinamide-modified hematopoietic progenitors to accelerate immune recovery and reduce infection risk in patients with hematologic malignancies.
Pluripotent stem cells
Cell therapies derived from pluripotent stem cells (PSCs), including embryonic and induced (iPSCs), show promise in clinical development for regenerative treatments. In cardiovascular disease, allogeneic PSC-derived cardiomyocytes are being tested through direct myocardial injection and in engineered cardiac patches for heart failure. In neurodegenerative disease, ESC- and iPSC-derived dopaminergic neurons are under investigation for Parkinson’s disease, including emerging autologous approaches using patient-specific iPSC-derived midbrain dopaminergic cells. For metabolic disorders, early clinical studies using iPSC-derived pancreatic islets and allogeneic ESC-derived islet infusions have shown encouraging improvements in glycemic control for patients with type 1 diabetes. Other PSC-derived cell therapies in development include retinal pigment epithelial cells and natural killer (NK) cells.
Non-stem cell therapies
Beyond stem cell–based approaches, non-genetic cell therapies using differentiated cell types continue to broaden the therapeutic landscape. Among these, immune cell therapies are particularly prominent, leveraging the body’s natural defense mechanisms to eliminate malignant or dysfunctional cells. Tumor-infiltrating lymphocyte (TIL) therapies, such as Amtagvi (lifileucel), employ naturally occurring T cells that recognize tumor antigens without genetic modification. Autologous TILs are expanded ex vivo from a patient’s own tumor, capitalizing on their inherent affinity for cancer cells. Additional examples include Rethymic, an allogeneic processed thymus tissue therapy that supports the development of functional T cells in athymic patients, and Provenge (sipuleucel-T), which activates autologous antigen-presenting cells ex vivo to trigger an immune response against prostate cancer.
Non-genetically modified cell therapies offer key advantages in safety, simplicity, and manufacturing efficiency. By avoiding viral vectors, gene-editing tools, and complex molecular validation, they streamline production, shorten development timelines, and reduce costs. Because their genomes remain unaltered, these therapies eliminate risks such as insertional mutagenesis, off-target effects, and unintended transgene expression, resulting in a more predictable safety profile, particularly for autologous products. Retaining their natural gene regulation and differentiation capacity, they also complement gene-modified and conventional treatments, broadening their therapeutic applicability across diverse diseases.
Regulatory Considerations
The US FDA takes a broad approach to safety testing when it comes to cell-based medical products. At the heart of its framework is the expectation that manufacturers rigorously demonstrate that their master cell banks are free from harmful contaminants. The agency’s recommendations in its 2024 draft guidance for human allogeneic cells span microbial, viral, and genetic testing, ensuring that risks are addressed before products reach clinical use.
Culture-based mycoplasma testing is essential, with flexibility for newer validated assay methods as long as they are proven to be equally sensitive. Beyond these basics, the FDA expects developers to screen for a wide panel of human viruses, from HIV and hepatitis to herpesviruses and polyomaviruses. The specific scope of testing is guided by the intended use of the cells, with special scrutiny applied if they are destined for immunocompromised patients. The agency also stresses the importance of testing for “adventitious viruses,” or unexpected or unknown viral contaminants. Traditional methods rely on exposing a sample to several different cell lines or even animal models, with any viral growth signaling a problem. High-throughput sequencing methods can also replace some of the more cumbersome animal-based tests, provided the method is carefully validated and its reliability explained to regulators.
Beyond infection risks, the use of genetic tools in modern cell therapy, such as reprogramming vectors or gene-editing systems, necessitates a need to check for leftover genetic material that could alter safety. The FDA recommends direct testing for residual vectors and, in the case of retroviral tools, additional safeguards to rule out the presence of replication-competent viruses. Whole genome sequencing is also encouraged, particularly for long-lived, highly expanded, or genetically modified cell lines, since it can reveal mutations, off-target editing, and other changes that might affect product safety.
Finally, tumor risk is an important consideration. Some cells, such as stem cells or cancer-derived lines, are naturally tumor-forming and not tested further. Others, especially primary or engineered cell lines, are expected to be evaluated for their potential to form tumors, unless data already show that the master cell bank is comparable to cells previously studied in preclinical models. By integrating safety testing strategies early and building development workflows around them, developers of cell-based therapies can not only streamline regulatory interactions but also strengthen confidence in the safety and reliability of their products.
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