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Two papers published in the current issue of Cell Transplantation (20:5), now freely available on-line at www.ingentaconnect.com/content/cog/ct/, highlight the therapeutic potential of human Sertoli cells that are present in the testes and are also called "nurse" or "mother" cells because they nurture the developing sperm cells. Sertoli cells form the blood-testes barrier that separates the blood compartment of the testes from the compartment of the seminiferous tubules. Once differentiated to form the blood-testes barrier, Sertoli cells do not proliferate, although recent research has been aimed at growing Sertoli cells outside of the body.
Determining Sertoli cell functionality in vitro
A team of U.S. and Argentina-based researchers reporting on isolating and characterizing Sertoli cells from deceased human organ/tissue donors report on techniques by which Sertoli cells "proliferated readily" in vitro under "optimized conditions" with a four day "doubling time."
"Since there is interest in using Sertoli cells to minimize transplant rejection due to their immunological suppressive properties, establishing conditions to produce proliferative human Sertoli cells in vitro could facilitate research on their use for therapeutic applications in cell or organ transplantation," said study corresponding author Dr. Constance M. John of San Francisco-based MandalMed, Inc. "In this study we aimed to isolate and expand primary adult human Sertoli cells from cadaveric testes and characterize them to determine their functionality in vitro."
The researchers found that expanded, cryopreserved Sertoli cells could retain their characteristic markers and exhibited prototype functionality to establish a tight junction barrier.
"The cells provided evidence of potential utility in spermatogenesis and infertility research and reproductive toxicology," concluded the researchers. "Because of their robust proliferative activity and unique biological role, the primary Sertoli cells could have cell therapy applications."
Citation: Chui, K. ; Trivedi, A. ; Cheng, C. Y.; Cherbavaz, D. B.; Dazin, P. F. ; Huynh, A. L. T.; Mitchell, J. B.; Rabinovich, G. A.; Noble-Haeusslein, L. J.; John, C. M. Characterization and Functionality of Proliferative Human Sertoli Cells. Cell Transplant. 20(5):619-635;_2011.
Sertoli cells successfully deliver therapeutics deep into the lung
In a study seeking a better way to get medication to lower lung areas, such as to the alveoli and other areas difficult to reach and in which to retain therapeutics, University of South Florida (USF) researchers report that rat Sertoli cells loaded with chitosan nanoparticles and coupled with an anti-inflammatory compound, injected into the tails of mice with deep inflammation, reached the deep areas of the lung quickly and stayed active.
Current lung therapy techniques, such as aerosols, nebulizer mists, Metered Dose Inhalers and other means have proven largely ineffective because of airway obstructions, mucus, and airway edema that often prevent inhaled delivery. Even when these therapeutics are delivered effectively, they are often quickly expelled during exhalation and the drug is not in the lung long enough for sustained release.
"A novel way to deliver nanoparticles coupled with drugs to the deep lung is to utilize a bio-compatible cell-based system and deliver therapy through the peripheral vasculature instead of a pulmonary route," said corresponding author Dr. Donald F. Cameron of the University of South Florida (USF) Department of Pathology and Cell Biology.
The USF study tested the delivery of an anti-inflammatory compound to the deep lungs of animals modeled with pulmonary inflammation and found a "high therapeutic effect" 24 hours after drug delivery.
"The drug-loaded Sertoli cells became entrapped in the host animal's deep lung and was distributed around the alveoli while intact Sertoli cells were not detected in other tissues or organs," said Dr. Cameron. "At 15 minutes post injection, 92 percent of the labeled nanoparticle load in the injected Sertoli cells were present in the lungs with a minimal amount detected in the liver and kidney."
The researchers concluded that the use of pre-loaded Sertoli cells to deliver therapeutic nanoparticles to the lungs through the peripheral vasculature and subsequently migrated to the pulmonary vasculature, potentially providing an effective therapeutic alternative to current methodologies that have been proven less effective.
"These two studies describe a set of conditions for expanding human sertoli cells in vitro from deceased organ/tissue donors and a potential use for the cells (this time taken from rats)" said Dr. Camillo Ricordi, coeditor-in-chief of Cell Transplantation and Director of the Cell Transplant Center and Diabetes Research Institute at the University of Miami. "While the second paper covers the potential use of sertoli cells as vectors for the delivery of specific factors to the deep areas of the lung, these cells may also be beneficial as delivery systems for other disorders. This will require further investigation."
Citation: Kumar, A.; Glam, M.; El-Badri, N.; Mohapatra, S.; Haller, E.; Park, S.; Patrick, L.; Nattkemper, L.; Vo, D.; Cameron, D. F. Initial Observations of Cell-Mediated Drug Delivery to the Deep Lung. Cell Transplant. 20(5):609-618; 2011.
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Dr. Constance M. John, MandalMed, Inc. 665 3rd St. Suite 250,
San Francisco, CA 94107
Tel. (415) 495-5570
Fax. (415) 495- 5575
Dr. D.F. Cameron, MDC 11, Department of Pathology & Cell Biology, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd. Tampa, FL 33612
Tel. (813) 974-9434
Fax. (813) 974-2058
Camillo Ricordi, MD
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