What are the practical, ethical, and pathobiological considerations in the use of minipigs as an animal model in drug discovery for acute radiation syndrome and delayed effects of acute radiation exposure?

Figures & data

Table 1. Minipig as a non-rodent model in drug discovery

Advantages	Disadvantages
Sexual maturity at early age (4–5 months) compared to NHPs (3–4 years). Acceptance by regulatory agencies increasing	Requires large quantities of drug and associated higher costs
Less sentinel compared to NHPs and canines	Difficulty in handling older adults due to their large size
Similarity to humans in organ anatomy and physiology, most popular for dermal and cardiovascular models and to test cardiac implantation devices	Labor intensive due to complex husbandry requirements compared to rodents
Commercially available for research and increasing availability of transgenic pigs	Limited availability of historical database/background data in preclinical safety
Excellent model for perinatal toxicology and nutritional studies due to similarity to human infant’s digestive system and nutritional requirements	Not ideal for long term studies (>4 – 6 weeks) due to higher rate of body weight gain
Easier serial blood sample collection for longitudinal studies compared to small animals	Limited availability of reagents and biomarkers
Shares same environment as that of humans and is exposed to similar atmospheric toxins and pollutants in air and water	Proteome, genome, and epigenome maps are not well characterized
Handling and drug dosing is easier compared with NHPs and canines	Longer lifespan and higher maintenance costs compared to rodents
Small size compared to conventional swine breeds

NHPs – nonhuman primates. Since there is limitation for the number of references in an editorial article, individual references for the above studies have not been cited.

Table 2. Minipig strains commonly used in drug discovery

Minipig strains	Body weight (kg)*	Details
Hanford miniature	25–40	Obtained by mating Pitman-Moore breeders with Palouse swine and a Louisiana swamp hog and later with introduction of Yucatan pigs. Widely used for cardiovascular studies due to similar heart size as humans
Miniature Yucatan	20–30	Developed at Colorado State University from foundation animals imported from Yucatan Peninsula of Mexico; model available for spontaneous ventricular septal defect
Micro Yucatan	14–20	Same as above
Sinclair/Hormel	16–22	First developed by Hormel Institute, Minnesota, United States, commonly used for cutaneous melanoma studies; histopathologically similar to humans
Göttingen	9–14	Most widely used experimental breed; developed at Georg-August-University in Göttingen, Germany, resulted from crossing Minnesota minipig, Vietnamese potbelly pig and German Landrace strains. Model for chronic heart failure and also for hematopoietic acute radiation syndrome
Bama miniature	8–12	Developed at Department of Animal Sciences, Third Military Medical University, China, Sows and boars obtained from original stock at Bama county, GuangXi Province, China
Wuzhishan minipigs	7–12	Outbred and cultivated in tropical areas of Hainan, China
CLAWN miniature	12–17	Originated from Central Laboratory of White Nipai (CLAWN, Japan), by crossing F1 progeny of Göttingen with Ohmini minipigs and subsequent mating with F1 progeny of Landrace and Yorkshire domestic pigs
NIBS minipigs	17–25	Developed at Nippon Institute for Biological Science, Japan, resulted from breeding three distinct breeds, Pitman-Moore, Chinese native and Göttingen
Meishan breed	~62	These are sub-groups of Taihu pigs, originated from Taihu Valley of lower Changjiang river basin, China, and were later imported to two laboratories in US (Iowa State and US FDA)
Ohmini	~25	Developed from Chinese breed at the Japan Domestic Animal Institute Co. Ltd, Japan
Mini-Lewi		Developed at Humboldt-University from a cross of Vietnamese Pot Belly pigs, Saddle Back pigs and German Landrace followed by consistent selection for small body weight
Libechov minipig		Libechov Institute of Animal Physiology and Genetics, Czech Republic because of the similarities between human and porcine skin, also a suitable transgenic model for Huntington’s disease
Pitman-Moore		Florida swamps were bred by Pitman-Moore pharmaceutical company
Ossabaw Island Hog		Derived from feral pigs on Ossabaw Island, Georgia, United States

*Approximate weights at sexual maturity (~4 – 6 months of age). Additional minipig strains that were used for biomedical research are: Guizhou minipig, Yorkshire, Pietran, Mulefoot Hog Breed, American Guinea Hog, FBM minipig, KuneKune Breed, Juliana Breed, and Pot-Bellied Pig. However, their actual body weight ranges and additional details were not available/verifiable. Since there is limitation for number of references in an editorial article, individual references for above studies have not been cited.

Table 3. Medical countermeasures evaluated against radiation injury using minipigs

Minipig strains	Radiation types/dose/dose rate	Radiation exposure	Medical countermeasure
Göttingen	γ-rays (^60Co); 2.2 Gy; 0.6 Gy/min	Total-body	Neulasta
Yucatan	Protons; 2 Gy	Total-body	Neulasta
Göttingen	γ-rays (^60Co); 1.78 Gy; 0.6 Gy/min	Total-body	Neupogen
Göttingen	γ-rays (^60Co); 50 Gy; 0.6 Gy/min	Partial-body (skin)	Autologous and allogenic ADSCs
Göttingen	γ-rays (^60Co); 50 Gy; 0.6 Gy/min	Partial-body (skin)	Sonic hedgehog transfected ADSCs
Göttingen	γ-rays (^60Co); 50 & 60 Gy; 0.6 Gy/min	Partial-body (skin)	Bone marrow derived MSCs
FBM minipigs	X-rays (LINAC); 90 Gy	Partial-body (skin)	Vascularized flap surgery + autologous BM derived MSCs
Miniature pig*	γ-rays; 15 Gy	Partial-body (parotid gland)	Sarcandra glabra powder
Miniature pig*	X-rays; 36 Gy	Partial-body (parotid and sub-mandibular glands; 6 × 6 Gy in 3 weeks)	Orciprenaline and carbachol
Minipig*	X-rays (LINAC); 37.5 Gy; 3.2 Gy/min	Partial-body (salivary gland; 7.5 Gy x 5 days)	Rapamycin
Miniature pigs*	X-rays (LINAC); 30 Gy; 3.2 Gy/min	Partial-body (oral cavity; 6 Gy x 5 days)	Tempol
CLAWN miniature pig	X-rays, 10 Gy; 1.2059 Gy/min	Partial-body (skin)	Basic fibroblast growth factor
Guizhou minipig	20 Gy (LINAC); 3 Gy/min	Partial-body (dorsal Skin)	hPDGF-A expressing BM derived MSC and skin-derived keratinocytes
Göttingen	γ-rays (^60Co); 50 Gy; 1.301 Gy/min	Partial-body (dorsal skin)	Curcumin
Göttingen	x-rays (LINAC); 1.2 Gy; 0.6 Gy/min	Total body + full thickness skin burn	Autologous ADCSs

* Minipig strain not specified in the respective publication. ADSCs – adipose-derived stem cells; hPDGF-A – Human platelet-derived growth factor-A; LINAC – linear accelerator; MSCs – mesenchymal stem cells; TBI – total-body irradiation; Since there is limitation for number of references in an editorial article, individual references for above studies have not been cited.