Table 1.
Pre-clinical bone marrow transplantation studies.
| Study [Reference] |
Animal Model | HSCT Protocol | Evaluation Time after BMT | Clinical Evaluation and Outcomes | Histopathological/Laboratory Assessment |
|---|---|---|---|---|---|
| Ikehara, S. et al., 1985 [8] |
Mice; strains with spontaneous SLE-like disease | Conditioning: TBI (850–950 rads from a cobalt-60 source) Reconstitution: IV injection of 2 × 107 allogenic BM cells from young healthy mice BMT either (1) before or (2) after AD onset |
3 and 5 months | (1) Mice in pre-AD state (BMT before disease onset): no development of thymic abnormalities and AD up to month 5; (2) Mice with evidence of AD and lymphadenopathy at BMT: survival beyond month 3 after BMT. |
(1) no development of thymic abnormalities (histological examination); (2) disappearance of lymphadenopathy and marked amelioration of lymphoid cell infiltrations into the kidney and liver; marked reduction of glomerular deposits of IgG, IgA, C3, and gp70 (immunofluorescence); reduced levels of CICs and anti-dsDNA ab. |
| van Bekkum, D. W. et al., 1989 [9] |
Rats; inbred strains Buffalo and Wag/Rij, with induced AA a | Conditioning: TBI (850 cGy) Reconstitution: IV injection of 5 × 107 BM cells from syngeneic (Buffalo) or allogeneic (Wag/Rij) sex-matched donors BM cells collection: suspension by flushing of femoral bones cavities with Hanks’ salt solution |
Weekly observation (arthritic score) up to: −14 w after syngeneic BMT −9 w after allogenic BMT. |
Clear-cut complete regression of arthritis (expressed as a gradual decrease of paw thickness) in BMT-treated groups compared to controls. | Absence of inflammatory reaction in treated rats at 4 weeks after BMT versus classical severe inflammation and destruction process in control rats (histological examination). |
| Karussis, D. M. et al., 1992 [12] | SJL/J mice with induced EAE b | Conditioning regimens (three groups): (1) TBI (900 cGy) (2) TBI (1100 cGy) (3) Cy (300 mg/kg) Reconstitution: syngeneic BM cells |
3 months | (1) delayed onset and reduction in incidence and severity of EAE; (2) reduced incidence of EAE (developed in 1/7 treated mice); (3) no development of EAE, and resistance to rechallenge with the same encephalitogenic inoculum. |
Lymphocytes obtained from treated mice did not proliferate in vitro in response to myelin basic protein or tuberculin-purified protein derivative, contrary to controls. |
| van Gelder, M. et al., 1993 [13] | Buffalo rats with induced EAE c | Conditioning: TBI (900 cGy) Reconstitution: syngeneic BM cells from healthy donors. |
- | In mice with already developed severe paresis before BMT, greatly accelerated recovery of paresis compared with untreated controls. | N.R. |
| Pestronk, A. et al., 1983 [14] |
Female Lewis rats with induced EAM d | Conditioning: TBI (600 rads from a dual-source cesium 137 irradiator) + Cy (200 mg/kg) Reconstitution: IV reinfusion of 6 × 107 autologous BM cells BM cells collection: autologous femur, tibia, spleen, and lymph nodes, washed twice and suspended in RPMI. |
8 weeks | N.R. | Prompt and sustained fall in the levels of serum ab against both foreign (Torpedo), and self (rat) AChR: −titre of ab against Torpedo AChR reduced to 2% of pre-treatment levels at 8 weeks; −titre of auto-ab against rat AChR fell to undetectable levels within 2–3 weeks and did not rise subsequently. |
a AA obtained with the intradermal injection of a suspension of M. tuberculosis in incomplete Freund’s adjuvant. b EAE induced by immunisation with spinal cord homogenate in adjuvant. c EAE induced by immunisation with syngeneic spinal cord homogenate in complete adjuvant. d EAMG obtained by immunisation with a first injection of 50 μg of AChR (from the electric organ of Torpedo californicus), emulsified in 50 μg adjuvant and rechallenge injections. In this model, rats did not develop weakness but expressed AChR ab. Abbreviations: AA, adjuvant arthritis; ab, antibodies; AChR, anti-acetylcholine receptor; AD, autoimmune disease; BM, bone marrow; BMT, bone marrow transplantation; cGy, Centigray; Cy, cyclophosphamide; EAE, experimental autoimmune encephalomyelitis; EAMG, experimental autoimmune myasthenia gravis; CICs, circulating immune complexes; Ig, immunoglobulin; N.R., not reported; SLE, systemic lupus erythematosus; TBI, total-body irradiation; w, weeks.