Microencapsulation of Leydig cells: a system for testosterone supplementation.
The use of testosterone supplementation for elderly men has increased markedly over the last decade due to a recognized gradual decline in serum testosterone, which may lead to decreased bone mass, muscle strength, and libido. Testosterone supplementation is also used widely to treat some forms of erectile dysfunction, androgen deficiency, and infertility. However, long-term exogenous testosterone therapy has been associated with several complications, such as fluid retention, nitrogen retention, and hypertension. Due to these problems, alternate treatment modalities, involving more physiological and longer-acting systems for androgen delivery, have been pursued. Alginate-poly-L-lysine-encapsulated Leydig cell microspheres were used as a novel method for the delivery of testosterone in vivo. Encapsulated Leydig cells, which were stimulated with human chorionic gonadotropin, secreted high levels of testosterone in culture. Unencapsulated cells injected i.p. or s.c. failed to produce any testosterone levels, even with human chorionic gonadotropin stimulation. Castrated rats that were administered encapsulated Leydig cells i.p. or s.c. maintained a serum testosterone level between 0.23 and 0.51 ng/ml. Similar levels of testosterone were obtained for 43 d when the encapsulated Leydig cells were injected s.c. (0.28-0.48 ng/ml). Approximately 10% of a normal adult rat Leydig cell population was injected into each castrated animal; however, this resulted in serum testosterone levels of up to 40% of normal. Clinically, testosterone is usually delivered for supplementation and not for full replacement therapy. Therefore, the findings of this study suggest that microencapsulated Leydig cells may be a viable option as a therapeutic modality involving testosterone supplementation.
Machluf
Marcelle
M
Laboratory of Cellular Therapeutics and Tissue Engineering, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Orsola
Anna
A
Boorjian
Stephen
S
Kershen
Richard
R
Atala
Anthony
A
D000464:Alginates; D000818:Animals; D001672:Biocompatible Materials; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D008863:Microspheres; D009919:Orchiectomy; D011107:Polylysine / Q000031:analogs & derivatives*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000008:administration & dosage* / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism
D000464:Alginates; D001672:Biocompatible Materials; C051546:alginate-polylysine-alginate; D011107:Polylysine; D013739:Testosterone