Rotator cuff tendinopathy is a major cause of morbidity in our ageing population. No effective drug therapies are available. An urgent need exists for regenerative repair strategies to prevent further tendon degeneration and ameliorate existing pathology. Mesenchymal stem/stromal cells are touted as an effective therapy in a plethora of chronic diseases. In order to progress to a rational therapy of patients with rotator cuff injury, we aim here to isolate cell populations from human tissues and compare their effects in an in-vitro model of tendon degeneration induced by stress-deprivation (SD). Human stromal cell preparations (HSC, n=6 patients) were isolated from bone chip explants (knee/hip joint replacement) and grown in culture to the 3^rd/ 4^th passage, when cells were tested for multipotency (adipo-, osteo- and chondro-genesis) and co-cultured with freshly harvested sheep infraaspinatus tendon explants for 1 and 5 days. Total RNA was extracted from ex-vivo tendon and tendon cultured ± cells and used in real time RT-PCR with ovine-specific primers for matrix proteins, enzymes, inhibitors and mediators.All HSC preparations were capable of forming chondrocytes, osteoblasts and adipocytes. Genes with significantly increased expression in SD tendon (compared to ex-vivo) included COL1A1, ADAMTS4, TNMD, TGFB and IL8. The increased expression of all of these genes was moderated by one or more, but not all, HSC lines. Tendon genes with significantly decreased expression after SD included COL2A1, DCN and FMOD; these changes were exacerbated by 1 to 4 HSC preparations. A further 10 gene changes induced by SD were not affected by any HSC.Despite having a stable phenotype and properties of multipotent stem cells, these HSC preparations from different individuals had variable efficacy in ameliorating gene expression changes in tendon induced by SD. Further work is required to understand the molecular basis of tendinopathy before therapeutic autologous cell injections can be recommended.