Ann Rehabil Med.  2012 Apr;36(2):197-206. 10.5535/arm.2012.36.2.197.

The Effect of Human Placental Extract on Rheumatoid Arthritis in an Animal Model

• Park JD
• Lee SI
• Kim AR
• Park JM
• Shin SY
• Shin JH
• Moon SW
• Park H
• Oh MK
• Shin HS

• KMID: 2266757
• DOI: http://doi.org/10.5535/arm.2012.36.2.197

Abstract

OBJECTIVE
To assess the efficacy of human placental extract (HPE) in an animal model of rheumatoid arthritis (RA). METHOD: We used (i) KRN C57BL/6 TCR transgenic x NOD mice (KBx/N) serum transfer arthritis and (ii) collagen-induced arthritis (CIA) mice to evaluate the effi cacy of HPE (1 ul or 100 ul, intra-peritoneal, three times per week) on RA. Incidence, severity of arthritis, and hind-paw thickness were quantifi ed. Joint destruction was analyzed using modifi ed mammographic imaging. Histopathological analysis for inflammation, cartilage, and osteoclasts was performed using Hematoxylin-eosin (H-E), safranin-O, and tartrate-resistant acidic phosphatase (TRAP). ELISAs were used for detection of various cytokines in serum and joint tissue.
RESULTS
There were no significant differences in incidence of arthritis, clinical scores of arthritis, and hind-paw thickness between HPE-treated and vehicle-treated groups for up to 2 weeks in the KBx/N serum transfer arthritis model. Histopathological analysis also showed no differences 2 weeks after treatment. Levels of TNF-alpha, IL-1beta, IL-6, IL-10, and RANKL in serum and joint tissues were similar in all groups. Furthermore, there were no differences in clinical, radiological, and histological parameters between HPE-treated and vehicle-treated group for 3 weeks in the CIA model.
CONCLUSION
Systemic treatment with HPE has no beneficial effects on arthritis in animal models of RA. Therefore, indiscreet use of HPE in RA should be forbidden.

Keyword

Human placental extract (HPE); Rheumatoid arthritis (RA)

MeSH Terms

Animals
Arthritis
Arthritis, Experimental
Arthritis, Rheumatoid
Cartilage
Cytokines
Enzyme-Linked Immunosorbent Assay
Humans
Incidence
Inflammation
Interleukin-10
Interleukin-6
Joints
Mice
Mice, Inbred NOD
Models, Animal
Osteoclasts
Tumor Necrosis Factor-alpha
Cytokines
Interleukin-10
Interleukin-6
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 Effects of human placental extract (HPE) on arthritis in the KBx/N serum transfer model. (A) The cumulative incidence of arthritis during the course of the experiment in vehicle (n=10), HPE 1 ul (n=10), and HPE 100 ul (n=10) treatment groups. The severity of arthritis (B), hind-paw thickness measurement (C), and the change of body weight (D) in each group are presented. Values presented are the mean±SEM for each experiment.

• 

  Fig. 2 The histopathological assessment of KBx/N serum transfer arthritic mice treated with human placental extract (HPE). (A) Representative H&E staining (upper row, original magnification ×40), safranin O (middle row, ×40), and TRAP (lower row, ×400) stained joint tissue sections from vehicle (n=10), HPE 1 ul (n=10), and HPE 100 ul (n=10) treatment groups. (B) Histopathological scores of synovial inflammation, cartilage damage, and bone erosion in each group. (C) The total number of TRAP-positive cells in the field was counted in each group. Values presented are the mean±SEM.

• 

  Fig. 3 Effects of human placental extract (HPE) on cytokines in sera (A) and joint homogenates (B) of KBx/N serum transfer arthritic mice. Sera and hind paws were collected at the termination of the experiment (day 14) in vehicle (n=10), HPE 1 ul (n=10), and HPE 100 ul (n=10) treatment groups. The concentrations of various cytokines were analyzed by ELISA methods. Values presented are the mean±SEM.

• 

  Fig. 4 Effects of human placental extract (HPE) on collagen-induced arthritis (CIA). The severity of arthritis (A) and hind-paw thickness measurement (B) of CIA mice treated with vehicle (n=8) or HPE 1 ul (n=8). Values presented are the mean±SEM for each experiment.

• 

  Fig. 5 The radiological and histopathological assessment of CIA mice treated with human placental extract (HPE). (A) Representative radiograph (upper row) and H&E (lower row, original magnification ×40) of vehicle or HPE injected CIA mice. (B) Bone destruction was quantified in knee and ankle joints from CIA mice in each group. (C) Histopathological scores of synovial inflammation, cartilage damage, and bone erosion in each group. Values presented are the mean±SEM.

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