Of (Spiny) Mice and Men

The four stages of mammalian wound healing

In response to an injury, the classical wound healing process progresses through four key, often overlapping, stages (Figure 1):⁴

1. Hemostatic Phase – Occurring immediately after an injury, this platelet-mediated process results in clot formation (a provisional matrix) and the cessation of bleeding from damaged vasculature. 
2. Inflammatory Phase – An immune-driven process in which neutrophils and macrophages migrate to the wound site in response to chemokines secreted by local cells (i.e., tissue-resident macrophages and dendritic cells). These cells clear debris and dead cells, phagocytize invading microbes, and produce growth factors that drive the subsequent proliferative stage.    
3. Proliferative Phase – This phase is characterized by the expansion and migration of multiple cell types to restore integrity. Endothelial cells migrate to the wound site and promote angiogenesis; proliferating keratinocytes from the wound margins drive re-epithelialization; and proliferating fibroblasts from nearby dermis generate granulation tissue, an immature connective tissue that replaces the provisional matrix formed by the clot during hemostasis. 
4. Maturation and Remodeling Phase – During this final stage, fibroblasts differentiate in response to mechanical forces and biochemical differentiation factors. Their contractility assists in physical wound closure. Fibroblast secretion also shifts to increased production of collagen I, which replaces the weaker collagen III present in granulation tissue, with collagen fibers becoming increasingly parallel to the wound bed. This results in a fibrotic scar—an area of intact skin with reduced strength, altered pigmentation, and a lack of hair follicles or sebaceous glands.    

Figure 1: Cross-sectional overview of wound healing stages. Wound healing proceeds through hemostatic, inflammatory, proliferative, and maturation/remodeling phases, progressing from clot formation and immune cell recruitment to re epithelialization, granulation tissue deposition, and finally myofibroblast mediated contraction and collagen remodeling that culminates in scar formation. Created with BioRender.com.

The spiny mouse: A mammalian model of scarless regeneration

The classical, four-stage wound healing framework described above has long been regarded as the default outcome for mammalian tissue repair. While there are examples of extraordinary wound healing or even limb regeneration in reptiles and amphibians, mammalian injuries have historically been thought to always involve some degree of incomplete regeneration and fibrotic scarring. The spiny mouse (Acomys spp., with Acomys cahirinus the most commonly studied species) fundamentally challenges this assumption, demonstrating that complete, scarless regeneration is possible within a mammalian context.

Acomys species have evolved this regenerative capacity as a functional survival strategy. These small desert rodents—more related to gerbils than mice—use this regenerative ability as an anti-predation measure. When attacked, large sections of their spine-covered skin can tear off easily, akin to certain lizards dropping their tail or a limb.¹⁰ This technique, known as autotomy, allows Acomys the chance to escape a predator and live to fight another day. Acomys leverage typical mammalian wound healing mechanisms, yet are somehow able to completely regenerate even large, full-thickness wounds. 

Scarless wound healing in Acomys is an active area of regenerative biology research. While much of the literature concerning Acomys wound healing has primarily focused on their differences compared to that of mice (Mus musculus), insights gained from Acomys wound healing have significant translational potential for human regenerative medicine. Following an injury, Acomys quickly achieves hemostasis and wound closure,⁵ accompanied by rapid re-epithelialization. This regenerative behavior is replicated in vitro by scratch assay, with primary Acomys keratinocytes closing scratch-assay wounds more rapidly than primary Mus keratinocytes.⁶

The inflammatory phase also appears to be reduced in Acomys with surprisingly low numbers of macrophages in the wound bed compared to Mus, as well as a lower ratio of pro-inflammatory macrophages.⁷ The proliferative and remodeling phases in Acomys are marked by a lower density granulation tissue, driven in part by elevated collagen III expression relative to Mus² The Acomys wound exracellular matrix (ECM) is further characterized by comparatively low levels of Col12a and high levels of matrix metalloproteases, all indicative of active ECM remodeling.^8,9 Further research into these regenerative mechanisms relies heavily on access to Acomys and derived tissue and cell models.   

Advancing Acomys wound healing research through accessible in vitro models

Given the relative rarity of Acomys colonies in research labs and the difficulties involved in their maintenance,¹⁰ there is a low supply of Acomys and Acomys cells available to researchers.  Studies have been conducted mostly in vivo, with in vitro work limited to freshly isolated primary cells with limited replicative potential. To make research more accessible, two primary Acomys dermal fibroblast lines were recently immortalized, characterized, and deposited with ATCC:¹¹

• AcoSI (ATCC® CRL-3579™) – an Acomys cahirinus dermal fibroblast line from a 2-day-old male neonate that was spontaneously immortalized by extended culture.   
• AcoSV40 (ATCC® CRL-3578™) – an Acomys cahirinus dermal fibroblast line from a 2-day-old female neonate that was immortalized by transduction with SV40 Large T-antigen and subsequent selection.

Both AcoSI and AcoSV40 replicate indefinitely while still maintaining the phenotype of primary Acomys dermal fibroblasts (pAFs), as independently confirmed by ATCC.⁸ These immortalized lines preserve key fibroblast characteristics, including fibroblast-like morphology, vimentin expression, and alpha smooth muscle actin expression, consistent with pAFs. Functional characterization further demonstrates that AcoSI and AcoSV40 exhibit comparable traction forces both to each other and to pAFs, as measured by traction force microscopy. Importantly, mass spectrometry of cell-derived matrices (CDM) generated by these cell lines revealed that their ECM is remarkably similar to that of pAFs, underscoring their relevance as in vitro models for regenerative wound healing studies.⁷

Because many regenerative differences between Acomys and Mus are mediated fibroblast-driven processes such as ECM deposition, remodeling, and immune regulation,¹² immortalized Acomys fibroblasts represent an invaluable tool for in vitro studies on scarless wound healing. Unlike primary cells, the immortalized lines AcoSI and AcoSV40 provide reproducible, off-the-shelf tools for mechanistic studies and therapeutic discovery. ATCC is proud to offer these unique cell lines to expand access to Acomys research and accelerate advances in regenerative wound healing.

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ATCC offers hundreds of human and animal cells of dermal origin, including primary and hTERT-immortalized primary cells and reporter-labeled cell lines.

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References

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10. Haughton CL, et al. The Biology and Husbandry of the African Spiny Mouse (Acomys cahirinus) and the Research Uses of a Laboratory Colony. J Am Assoc Lab Anim Sci 55(1): 9-17, 2016. PubMed: 26817973
11. Dill MN, et al. Generation and characterization of two immortalized dermal fibroblast cell lines from the spiny mouse (Acomys). PloS One 18(7): e0280169, 2023. PubMed: 37418364
12. Dill MN, et al. Exploring the Unique Extracellular Matrix Composition of Acomys as a Potential Key to Resisting Fibrosis. ACS Biomater Sci Eng 11(6): 3616-3633, 2025. PubMed: 40407745