Although several types of human skin substitutes are currently available, they usually do not include important skin appendages such as hair follicles and sweat glands, or various skin-related cells, such as dermal adipocytes and sensory neurons. This highlights the need to improve the in vitro human skin generation model for use as a tool for investigating skin diseases and as a source of cells or tissues for skin regeneration. Skin organoids are generated from stem cells and are expected to possess the complexity and function of natural skin. Here, we summarize the current literatures relating to the “niches” of the local skin stem cell microenvironment and the formation of skin organoids, and then discuss the opportunities and challenges associated with multifunctional skin organoids.

Dear Editor, Acquired lymphedema is a complex disease caused by cancer treatment or parasitic infection and few effective treatments are available for lymphedema. [1][2][3] It is urgently needed to develop new experimental approaches and therapeutic strategies. 3 In this study, we address a new role and mechanism of MSC-ex (human umbilical cord Wharton's jelly mesenchymal stem cells derived exosome) in lymphedema treatment. We found that MSC-ex delivered Ang-2 (angiopoietin-2) promoted lymphangiogenesis by upregulating Prox1 (Prospero Homeobox 1) mediated Akt signaling. MSC-ex can improve lymphatic function and ameliorate edema in a mouse model of acquired lymphedema.MSC-ex were isolated from the conditional medium of WJ-MSC, which were negative for CD206 and positive for CD29, CD44 (Figure 1A,D). Exosomal markers CD9, CD63, CD81, and TSG101 were expressed in MSC-ex, whereas Calnexin was not detected (Figure 1B,C). MSC-ex showed a spheroid shape, and the size was about 130 nm (Figure 1E-G). To investigate the effect of MSC-ex on edema, we developed an acquired lymphedema model via surgical dissection of lymphatic vessels in the mouse tail (Figure 1H). As shown in Figure 1I, subcutaneously administered Dir labeled MSC-ex localized in the injured tail at 24 h after treatment. MSC-ex treatment promoted lymphatic drainage in lymphedema mice as injected methylene blue across the site of incision at week 6, which was not found in PBS treated mice (Figure 1J). The edema determined by tail diameter was persisted in mice treated by PBS. However, the edema was markedly reduced at week 2 in mice treated by MSC-ex (Figure 1K). As lymphangiogenesis is crucial in lymphedema development after lymphatic ablation, 4,5 we analyzed the lymphatic anatomy and lymphangiogenesis in MSC-ex treated animals. Relative to PBS-treated animals, a relatively thinner dermis and epidermis was found in MSC-ex treated mice (Figure 1L). Number of LYVE-1 + (lymphatic endothelial hyluronan receptor-1) lymphaticsThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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