Regenerative medicine and tissue engineering aim to restore, replace, or regenerate human cells, tissues, and organs. This ambitious field combines biology, materials science, and clinical medicine to create solutions for conditions that cannot be fully treated with conventional therapies. At the foundation of much of this work are immortalised cell lines, which offer a reproducible and accessible resource for testing biomaterials, evaluating stem cell therapies, and modelling tissue repair.
While they do not fully replicate the complexity of primary human tissues, cell lines remain indispensable for early-stage research, providing scalable models to screen materials, evaluate cell–cell interactions, and explore how tissues respond to regenerative interventions. The following sections highlight ten key cell lines and their roles in shaping regenerative medicine.
HeLa Cells and Cellular Plasticity
The immortal HeLa cells, derived from cervical carcinoma, were not developed for regenerative purposes but have nevertheless influenced the field by demonstrating cellular plasticity. Their capacity for indefinite proliferation showcased how cells could escape senescence, sparking interest in pathways that might be harnessed for regenerative therapies.
In regenerative research, HeLa cells have contributed to:
- Biomaterial compatibility testing, where scaffolds are evaluated for cytotoxic effects.
- Studies of extracellular matrix interactions, clarifying how cells adhere, spread, and remodel their environment.
- Insights into telomerase activity, a critical enzyme for maintaining long-term cell viability in regenerative applications.
Although not a direct model for tissue repair, HeLa cells illustrate how manipulating cellular longevity and division may inform regenerative strategies.
HEK293 and Gene-Modified Regeneration
HEK293 cells, derived from embryonic kidney tissue, are widely used in gene engineering — a cornerstone of regenerative medicine. Their high transfection efficiency makes them excellent hosts for delivering genes that promote tissue regeneration or enhance stem cell differentiation.
Key roles include:
- Gene therapy vectors, where HEK293 systems are used to produce viral carriers for regenerative gene delivery.
- Testing regenerative signalling pathways, such as growth factors that drive tissue repair.
- Engineering cell–biomaterial interactions, introducing patient-specific mutations to study regenerative potential.
By enabling genetic modification, HEK293 supports precision-engineered regenerative approaches where therapies are tailored to specific tissues and patient needs.
CHO Cells and Biologics for Tissue Repair
In regenerative medicine, CHO cells are critical for producing biologics that aid tissue repair. Their ability to manufacture recombinant proteins with human-like glycosylation ensures that growth factors, cytokines, and structural proteins can be produced at scale for regenerative applications.
CHO-based systems contribute to:
- Production of therapeutic growth factors, such as vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMPs).
- Manufacture of scaffolding proteins, including collagen fragments used in biomaterial design.
- Customised biologics, ensuring protein therapies are adapted to regenerative requirements.
By serving as the industrial backbone of biologics production, CHO cells support the development of regenerative medicines that require high-quality protein products.
SH-SY5Y and Neuronal Regeneration
For neurological regeneration, SH-SY5Y cells provide a scalable model of neuronal differentiation. Their ability to develop axon-like projections and synaptic markers makes them suitable for investigating strategies to repair neuronal circuits.
In regenerative neurology, SH-SY5Y lines are used to:
- Model neuronal repair mechanisms, exploring axonal regrowth and synaptic recovery.
- Test neuroprotective agents, which support neuron survival after injury.
- Evaluate biomaterial scaffolds, such as hydrogels, designed to encourage neuronal adhesion and outgrowth.
Although they are tumour-derived, SH-SY5Y cells provide valuable early-stage insights into therapies aimed at repairing spinal cord injuries, neurodegeneration, or stroke damage.
MCF7 and Endocrine Regeneration
The MCF7 breast cancer line has unexpected relevance in regenerative medicine, particularly for endocrine and reproductive tissue modelling. Because they retain oestrogen receptor activity, MCF7 cells provide insights into how hormones regulate tissue growth and repair.
Applications include:
- Exploring oestrogen’s role in tissue regeneration, particularly in bone and reproductive systems.
- Testing biomaterials for endocrine compatibility, ensuring scaffolds do not disrupt hormone signalling.
- Assessing endocrine-disrupting chemicals, which can impair regenerative processes in hormone-sensitive tissues.
This hormone-responsive line underscores how endocrine signalling influences tissue repair, guiding regenerative strategies in hormone-dependent systems.
THP1 and Immune-Regenerative Interactions
The immune system plays a pivotal role in tissue repair, and THP1 cells provide an accessible model for macrophage function in regenerative medicine. By differentiating into macrophage-like cells, THP1 lines allow researchers to explore how immune activation influences healing.
In regenerative contexts, THP1 systems are used to:
- Study macrophage polarisation, which determines whether inflammation supports or hinders regeneration.
- Test immunomodulatory biomaterials, designed to control immune responses during tissue repair.
- Evaluate infection risks, modelling how pathogens may disrupt regenerative therapies.
THP1 cells highlight the importance of immune balance, showing that successful regeneration often depends on modulating inflammatory processes.
A2780 and Regeneration in Oncology Contexts
While primarily an ovarian cancer model, A2780 cells offer insight into how tissue regeneration and cancer biology intersect. Because regenerative signals can sometimes overlap with oncogenic pathways, A2780 systems help clarify the boundary between controlled repair and uncontrolled growth.
Research with A2780 has focused on:
- DNA repair pathways, which influence both tissue regeneration and cancer resistance.
- Chemotherapy-induced tissue damage, exploring how normal regenerative processes are impaired during treatment.
- Testing regenerative adjuvants, such as growth factors, in tumour-prone contexts.
These studies illustrate the caution required in regenerative medicine, where interventions must promote healing without encouraging tumour development.
HL-60 and Haematopoietic Regeneration
HL-60 cells, capable of differentiating into granulocytes or monocytes, serve as a valuable model for blood and immune regeneration. Haematopoietic recovery is critical after bone marrow transplantation or chemotherapy, and HL-60 provides insights into this process.
They are used to:
- Model immune cell regeneration, clarifying energy demands during haematopoietic recovery.
- Evaluate regenerative therapies, such as cytokines that stimulate bone marrow recovery.
- Screen drugs for haematotoxicity, which can impair regenerative capacity.
HL-60 studies contribute to strategies that enhance blood cell recovery, a central goal in regenerative haematology.
Caco-2 and Intestinal Regeneration
The colon carcinoma-derived Caco-2 line is a cornerstone for gastrointestinal regeneration research. When cultured, they form enterocyte-like cells with tight junctions, making them excellent models of intestinal repair.
In regenerative medicine, Caco-2 cells are used to:
- Test biomaterials for gut healing, such as scaffolds designed for intestinal reconstruction.
- Evaluate nutrient uptake restoration, critical for patients recovering from gastrointestinal surgery.
- Study epithelial regeneration mechanisms, including stem cell contributions to gut repair.
By replicating barrier function, Caco-2 cells support therapies aimed at restoring gastrointestinal health after injury or disease.
HepG2 and Liver Regeneration
As the liver is renowned for its regenerative capacity, HepG2 cells are widely used to study hepatic repair mechanisms. Though not fully equivalent to primary hepatocytes, they provide a scalable system for exploring regenerative processes in the liver.
Applications include:
- Investigating hepatocyte proliferation, central to liver regeneration after injury.
- Testing hepatoprotective compounds, which promote recovery in liver disease.
- Biomaterial evaluation, examining scaffolds designed for liver tissue engineering.
HepG2-based studies contribute to regenerative hepatology, where therapies aim to restore liver function in conditions such as cirrhosis or fatty liver disease.
Conclusion
Regenerative medicine and tissue engineering rely on immortalised cell lines to explore how cells respond to biomaterials, growth factors, and regenerative cues. While no line can fully capture the complexity of patient-specific tissues, together they form a toolkit for evaluating strategies across multiple systems.
HeLa illustrates cellular plasticity, HEK293 supports gene-based regenerative approaches, and CHO provides biologics for repair. SH-SY5Y aids neuronal regeneration, MCF7 clarifies hormone influences, and THP1 models immune-regenerative interactions. A2780 demonstrates the overlap between repair and oncology, HL-60 informs haematopoietic recovery, Caco-2 replicates gut regeneration, and HepG2 highlights hepatic repair mechanisms.
By providing reproducible and scalable models, these lines advance the vision of regenerative medicine — a field where restoring tissues and organs becomes a clinical reality.