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Janjanin, Saša and Djouad, Farida and Shanti, Rabie M. and Baksh, Dolores and Gollapudi, Kiran and Prgomet, Drago and Rackwitz, Lars and Joshi, Arjun S. and Tuan, Rocky S. (2008) Human palatine tonsil: a new potential tissue source of multipotent mesenchymal progenitor cells. Arthritis Research & Therapy, 10 (4). ISSN 1478-6362 (Electronic) English abstract INTRODUCTION: Mesenchymal progenitor cells (MPCs) are multipotent progenitor cells in adult tissues, for example, bone marrow (BM). Current challenges of clinical application of BM-derived MPCs include donor site morbidity and pain as well as low cell yields associated with an age-related decrease in cell number and differentiation potential, underscoring the need to identify alternative sources of MPCs. Recently, MPC sources have diversified; examples include adipose, placenta, umbilicus, trabecular bone, cartilage, and synovial tissue. In the present work, we report the presence of MPCs in human tonsillar tissue. ----- METHODS: We performed comparative and quantitative analyses of BM-MPCs with a subpopulation of adherent cells isolated from this lymphoid tissue, termed tonsil-derived MPCs (T-MPCs). The expression of surface markers was assessed by fluorescent-activated cell sorting analysis. Differentiation potential of T-MPCs was analyzed histochemically and by reverse transcription-polymerase chain reaction for the expression of lineage-related marker genes. The immunosuppressive properties of MPCs were determined in vitro in mixed lymphocyte reactions. ----- RESULTS: Surface epitope analysis revealed that T-MPCs were negative for CD14, CD31, CD34, and CD45 expression and positive for CD29, CD44, CD90, and CD105 expression, a characteristic phenotype of BM-MPCs. Similar to BM-MPCs, T-MPCs could be induced to undergo adipogenic differentiation and, to a lesser extent, osteogenic and chondrogenic differentiation. T-MPCs did not express class II major histocompatibility (MHC) antigens, and in a similar but less pronounced manner compared with BM-MPCs, T-MPCs were immunosuppressive, inhibiting the proliferation of T cells stimulated by allogeneic T cells or by non-specific mitogenic stimuli via an indoleamine 2,3-dioxygenase-dependent mechanism. ----- CONCLUSION: Human palatine T-MPCs represent a new source of progenitor cells, potentially applicable for cell-based therapies. Actions (login required)
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Janjanin, Saša (2009) Izolacija i karakterizacija mezenhimskih matičnih stanica iz nepčanih tonzila. PhD thesis, Sveučilište u Zagrebu. Croatian abstract Mezenhimske matične stanice (MMS) su multipotentne progenitorske stanice podrijetlom od odraslih tkiva, koje imaju sposobnost diferencijacije u različita tkiva mezodermalnog podrijetla, uključujući kost, hrskavicu i masno tkivo. Danas se za istraživačke i terapijske svrhe MMS najčešće izoliraju iz koštane srži (KS-MMS), no problemi vezani uz njihovu primjenu uključuju morbiditet donorskog mjesta, malen broj izoliranih stanica za terapijske svrhe i slabljenje diferencijacijskog potencijala s povećanjem dobi davatelja. Sve navedeno razlog je potrazi za alternativnim i mlađim donorskim izvorima MMS. U ovoj se disertaciji prvi put predstavlja i opisuje izolacija MMS iz nepčanih tonzila. Izvršena je komparativna i kvantitativna analiza adherentnih stanica iz tog tkiva, nazvana tonzilarnim MMS (T-MMS). T-MMS su uspoređene s KS-MMS, dobro istraženim i karakteriziranim tipom MMS. Analiza površinskih biljega pokazala je da T-MMS nemaju CD14, CD31, CD34 i CD45, a da izražavaju CD29, CD44, CD90 i CD105 biljege, što je karakterističan fenotip KS-MMS. Poput KS-MMS, i T-MMS je bilo moguće diferencirati u adipocite, osteocite i hondrocite. Diferencijacijski potencijal T-MMS je analiziran histološkim i histokemijskim pretragama, te RT-PCR analizom ekspresije gena znakovitih za pojedina mezenhimska tkiva. Populacija stanica izoliranih iz tonzila na površini ne izražava MHC molekule II. razreda, što može omogućiti terapijsku primjenu alogenih T-MMS. S obzirom na jednostavan kirurški pristup i izostanak etičkih dvojba oko tonzilektomije, ljudske nepčane tonzile mogle bi se iskoristiti kao prikladan alternativni izvor mladih i brzo proliferirajućih progenitorskih stanica za bazična istraživanja i terapijske primjene. English abstract Mesenchymal stem cells (MSCs) are adult multipotent progenitor cells that have the ability to differentiate into lineages of mesenchymal tissues including cartilage, bone and fat. They were originally isolated from bone marrow (BM-MSCs), but current challenges of clinical application of BM-MSCs include donor-site morbidity, and low cell yields associated with age-related decrease in cell number and differentiation potential, underscoring the need to identify alternative sources of MSCs. In the present work, the presence of MSCs in tonsillar tissue is reported for the first time. We performed comparative and quantitative analyses of BM-MSCs with a subpopulation of adherent cells isolated from this lymphoid tissue, termed tonsil-derived MSCs (T-MSCs). Surface epitope analysis revealed that T-MSCs were negative for CD14, CD31, CD34 and CD45 expression and positive for CD29, CD44, CD90 and CD105 expression, a characteristic phenotype of BM-MSCs. Similar to BM-MSCs, T-MSCs could be induced to undergo adipogenic, osteogenic and chondrogenic differentiation. Differentiation potential of T-MSCs was analyzed histologically, histochemically and by RT-PCR for the expression of lineage related marker genes. T-MSCs did not express class II MHC antigens, suggesting a potential role as a human allogeneic cell source for cell-based therapies. Thus, human palatine tonsil-derived MSCs, which are easily accessible without ethical concerns, represent an attractive alternative source for adult progenitor cells or MSCs for basic research and future clinical applications. Actions (login required)