Bioengineering breakthroughs: The impact of stem cell models on advanced therapy medicinal product development

Table 1 Type of somatic cells employed in specific advanced therapy medicinal products (ATMPs)

ATMP	Intended use	Cells	Applications	Action in the tissue
GTMPs	The focus is primarily on the genetic material that is delivered into the patient’s cells to correct or replace defective genes	Terminally differentiated: T-cells	Often modified for cancer immunotherapy (e.g., CAR-T cells)	They can be performed in vivo (directly in the patient) or ex vivo (cells are modified outside the body and then reintroduced), which are leading to therapeutic, prophylactic, or diagnostic effect
		Hematopoietic stem cells	Used for genetic disorders affecting blood cells
SCTMPs	Can involve cells that have been manipulated to alter their biological characteristics for therapeutic purposes, not intended to be used for the same essential function(s) in the recipient as in the donor	Terminally differentiated: Like fibroblasts and chondrocytes	Which are used for repairing specific tissues	They can repair or replace damaged tissues or to treat diseases, which are leading to therapeutic, prophylactic, or diagnostic effect. Unlike GTMPs, somatic cell therapy does not necessarily involve genetic modification but rather the application of cells to restore function
		Mesenchymal stem cells: Isolated adult tissues	These cells are known for their ability to differentiate into various cell types and are used in regenerative medicine
		Induced pluripotent stem cells: These are reprogrammed adult cells	Can differentiate into any cell type, providing a versatile option for therapy
TEPs	Cells that are used in combination with scaffolds to create functional tissues, not intended to be used for the same essential function(s) in the recipient as in the donor	Progenitor: Such as those derived from stem cells	Can differentiate into specific tissue types	They are designed to repair, regenerate, or replace damaged tissues or organs
		Engineered: Cells that have undergone substantial manipulation to achieve desired characteristics	For tissue repair or regeneration

ATMP: Advanced therapy medicinal product; GTMP: Gene therapy medicinal product; SCTMP: Somatic cell therapy medicinal product; TEP: Tissue-engineered product; CAR-T: Chimeric antigen receptor T.

Table 2 Comparison between many aspects surrounding stem cells applied in advanced therapy medicinal products (ATMPs)

ATMPs	Degree of cell manipulation	Regulatory considerations	Clinical trial design	Surgical considerations
SCTMPs	Substantial manipulation	Often involves rigorous scrutiny of the manipulation processes and the resultant biological characteristics of the cells. Regulatory bodies require extensive data on safety and efficacy, particularly because these therapies may involve significant changes to the cells’ original functions. Clinical trials must demonstrate not only the safety of the therapy but also its therapeutic benefits in the intended patient population	Often include endpoints that assess both the manufacturing process and the therapeutic outcomes. This may involve feasibility studies to ensure that the cells can be successfully harvested, manipulated, and reintroduced to the patient. The complexity of these therapies necessitates close coordination between clinical teams and manufacturing facilities	The administration may require less invasive procedures, depending on the therapy. For instance, T-cell therapies can often be administered through infusion after manipulation outside the body
TEPs	Substantial manipulation	The focus is more on the engineering processes and the ability of the product to integrate and function in the body. The regulatory framework may emphasize the physical and biological properties of the engineered tissues, requiring evidence that they can effectively repair or replace damaged tissues	May be more focused on demonstrating the functional integration of the engineered tissues and their ability to restore tissue function. The design of these trials often involves assessing the physical and biological properties of the implanted tissues and their long-term performance in the body	Typically involves more complex surgical procedures for implantation, which can introduce additional risks associated with surgery, such as infection or complications from the surgical site. The success of these products is closely tied to the surgical technique and the patient’s ability to heal and integrate the new tissue

ATMP: Advanced therapy medicinal product; SCTMP: Somatic cell therapy medicinal product; TEP: Tissue-engineered product.