Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04

    • SM-164 br Engineering cell cell adhesion

    2018-10-26


    Engineering cell–cell adhesion to direct stem cell fate decisions The findings that we described above show that CDH2 and CDH11 play important roles in stem cell lineage specification, and therefore, could be used to develop technologies to control stem cell differentiation by exploiting cell–cell interactions. To this end, we propose the following strategies (Table 1) to capitalize on the effects of cadherin-mediated intercellular adhesion: (i) Engineering cadherin surfaces to control stem cell differentiation; and (ii) Engineering surface microtopology to control the extent of cell–cell adhesion and signaling.
    Monitoring intercellular adhesion mediated stem cell lineage specification in real time To this end, our laboratory developed LentiViral Arrays (LVA) to monitor gene or pathway activation during stem cell differentiation. We designed a novel lentiviral dual promoter vector (LVDP) vector that enables quantitative measurements of the activity of a gene promoter (Pr) or a transcription factor (TF) binding site (Response Element, RE) independent of the number of gene copies per cell (Tian and Andreadis, 2009). We also designed a second lentiviral vector (shLVDP) that enables dynamic monitoring of Pr/RE activity with concomitant gene knockdown in a doxycycline (Dox)-regulatable manner, thereby enabling discovery of genes that may be involved in stem cell differentiation (Alimperti et al., 2012). In addition, the envelope of lentiviral particles was engineered to bind covalently to fibrin hydrogels during polymerization (Padmashali and Andreadis, 2011; Raut et al., 2010), thereby enabling generation of lentiviral arrays (LVA) that were employed to measure the activity of several Pr/RE participating in the inflammatory response (Tian et al., 2010). More recently, we generated a library of Pr/RE to monitor MSC differentiation towards adipogenic, osteogenic, chondrogenic or myogenic lineages and used it to identify novel pathways that may be involved in lineage specification (Padmashali et al., 2014; Moharil et al., submitted for publication). Potentially, this technology may be combined with novel microfabrication methods to determine how the extent of intercellular adhesion influences stem cell specification decisions of adult stem cells, cancer stem SM-164 or hiPSC and potentially also the pluripotency networks that are critical for cellular reprogramming.
    Conclusion and future perspectives
    Acknowledgments This work was supported in part by a grant from the National Science Foundation (CBET-1403086) to S.T.A.
    Introduction Regenerative stem cell research is now rapidly moving toward the clinic and routine medical applications. With the number of Phase II and III trials growing, the conduct of multi-country clinical research collaborations is becoming increasingly important. These partnerships accelerate processes of clinical translation, and form the basis for marketing approval of new therapies in multiple countries (Martell et al., 2010). At present, however, the conduct of international stem cell trials is hampered by a high level of regulatory heterogeneity across countries, and the absence of internationally harmonized governance frameworks (Bubela et al., 2014). Even though drug regulatory authorities in the USA, the European Union and Canada have now initiated collaborations that focus on the convergence of regulatory procedures for cellular therapy products, globally harmonized regulatory procedures are far-off (Arcidiacono et al., 2012). Japan for instance, has recently introduced a fast-track approval path for stem cell therapies (Cyranoski, 2013), and in China and India drug regulatory agencies have at present only issued provisional regulations and regulatory guidelines whose legal power is limited (Sleeboom-Faulkner and Patra, 2011; Viswanathan et al., 2013; Rosemann, 2013). But complications arise also from the ongoing growth of unregulated stem cell treatments that are offered to patients without systematic proof of safety and efficacy in many countries (Lysaght and Sipp, 2014; Ogbogu et al., 2013). Lucrative business opportunities and the existence of regulatory grey areas have given rise to uncontrolled applications and the emergence of transnational entrepreneurial networks that advocate alternative forms of research regulation. Professional associations such as the International Cellular Medicine Society (ICMS), for example, have developed their own guidelines and IRB and accreditation services (Blasimme, 2013). These activities support experimental for-profit interventions with stem cells outside of the methodological format of the randomized controlled trial and independent from the review procedures of drug regulatory agencies (Rosemann, under review). This diversification of clinical research standards within and across countries makes efforts of international harmonization increasingly difficult.