LAUSR

Cell reprogramming is of great significance to biomedical science, especially in regenerative medicine application. The classical mode called indirect reprogramming is to obtain stem cells or induced pluripotent stem cells (iPSCs) and stimulate them to become mature differentiated cells, which has been applied in cardiac disease, neuron disease, etc. For example, with transfection of four transcriptional factors Oct4, Sox2, Klf4, and c-Myc (Yamanaka factors), somatic cells could be reprogrammed into iPSCs and further be stimulated to differentiate into mature functional cells (Takahashi and Yamanaka, 2006; Takahashi et al., 2007). In contrast with indirect reprogramming, direct reprogramming has received lots of attention in recent years, due to its unique advantage of fast, efficient, and low risk of tumorigenesis. Direct reprogramming refers to the application of transcription factor overexpression, noncoding RNA delivery, or small molecule delivery to promote the direct transformation of cells into target differentiated cells. In other words, compared with indirect reprogramming, direct reprogramming does not have to go through the stage of pluripotent stem cells or progenitor cells, whichmeans it is easier to perform during cell differentiation. Lately, direct reprogramming has been applied as a therapeutic strategy to many diseases. For example, in ophthalmology, with application of five small molecules, Mahato et al. successfully reprogrammed fibroblasts into rod photoreceptor-like cells in vitro, which were further transplanted to restore vision of blind mice (Mahato et al., 2020). In another study, direct reprogramming was applied to wound healing in vivo. Kurita et al. (2018) proved that with the introduction of a combination of four epidermal growthrelated factors into the wound site, cells inside the wound were reprogrammed into epidermal cells, which enabled non-invasive wound healing and the function of new born skin was the same as the normal skin. The greatest value of direct reprogramming is that it makes cell reprograming in vivo possible to perform (Sekiryu and Matsuda, 2021). The common method for in vivo reprograming rely on virusbased strategy, which transfect transcriptional factor gene into targeted cells. Themost common used vector for gene transfection could be classified as viral and nonviral vectors (Chong et al., 2021). Viral vector has the advantage of high efficiency of gene transfection, while exogenous genes may be inserted randomly into the host cell genome, which threatens the integrity and safety of the cell genome (Geis et al., 2017). Nonviral vectors, such as liposome and nanoparticle, could reduce the rate of host immunogenicity response, which has received more concerns recently. Wang et al. developed a novel nonviral delivery system for cardiac reprograming, which consists of nanoparticles and biofilm. In detail, to enhance the targeting efficiency of this system, mesoporous silicon nanoparticles were decorated with neutrophil-mimicking membranes, which was modified with folic acid peptide. With high efficiency delivery of miRNA1, 133, 208, and 499 in vivo, cardiac fibroblasts in myocardial Edited by: Bruce Alan Bunnell, University of North Texas Health Science Center, United States