This study investigates the possibility of engineering a stem cell niche for inhibition of stem cell transformation, while promoting stem cell growth necessary for regenerative therapies against cancer. Cancer therapy necessitates surgical resection of malignant tissues with consequent tissue regeneration, which may be accomplished by implanting biomaterial scaffolds containing or attracting multipotent stem cells such as mesenchymal stem cells (MSCs). However, this approach requires further development, as recent studies demonstrate that MSCs can become malignant due to abnormal signaling from interactions with cancerous microenvironments. Indeed, cancer reoccurrence is shown to derive from a subpopulation of stem cells. It is therefore desirable to design biomaterials that prevent abnormal MSC transformation while preserving favorable performance. There is also increasing need for quantitative methods probing abnormal cell transformation. In this study, we developed an in vitro carcinogenic model inducing aberrant MSC transformation by nickel sulfate, and applied multi-photon imaging-based quantitative analysis of nuclear protein (NuMA) distribution to evaluate relationships between nuclear structure and MSC transformation. Tyrosine-derived polycarbonates, copolymerized in various molar ratios with (i) lipophilic monomers, (ii) hydrophilic monomers, poly(ethylene glycol) (PEG), and (iii) negatively charged monomers (DT), were used to identify bioactive components influencing MSC transformation. We found DT, as opposed to PEG, to both promote MSC growth and reduce abnormal transformation. Our results suggest a new concept for biomaterial design in regenerative cancer therapy.