The Potential of a Hair Follicle Mesenchymal Stem Cell-Conditioned Medium for Wound Healing and Hair Follicle Regeneration

Abstract

The study elucidated the wound healing and hair regeneration properties of a conditioned medium prepared from the culture of human hair follicle mesenchymal stem cells (HFMSCs). The wound-healing effects of mesenchymal stem cell-conditioned medium (MSC-CM) were tested in vitro using scratch assays co-cultured with HaCaT keratinocyte and monitored through optical microscopy. The cell proliferation of HFMSCs and the HaCaT keratinocyte were observed in the presence of different kinds of drugs including UK5099, sodium L-lactate, lactate dehydrogenase-A, MSC-CM, caffeine, and caffeic acid. The hair regeneration properties were investigated in vivo by administrating the MSC-CM solutions to adult B6 mouse models. For quantification, hematoxylin and eosin staining were performed following euthanasia. In vitro results revealed that MSC-CM promotes dermal cell migrations and enhances proliferation of HFMSCs and HaCaT keratinocytes, demonstrating wound-healing properties. Moreover, when the MSC-CM solutions were applied to the shaved mouse skin, a dark area that expanded overtime was seen. Although no hair growth was found, histological analysis proved that a fat layer thickness increment was found under the mouse’s skin, ultimately projecting the formation of new hair growth. MSC-CM promotes the migration and proliferation of dermal keratinocytes that are beneficial for wound healing and hair growth. It is believed that MSC-CM can potentially serve as the basis of alternative therapeutic applications for wound closure and skin regeneration as well as hair growth stimulation and hair loss prevention in alopecia.

Application of Cell-Derived Extracellular Vesicles and Engineered Nanovesicles for Hair Growth: From Mechanisms to Therapeutics

“…Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation into various mesenchymal tissues (osteogenic, adipogenic, and chondrogenic cell lineages) and have been identified as a promising cell-based therapy for regenerative medicine ( Han et al, 2019 ; Shammaa et al, 2020 ). Several research groups have studied the stem cell therapies for treating hair loss including adipose-derived stem cells (ADSCs) ( Fukuoka et al, 2017 ), umbilical cord blood-derived MSCs ( Oh et al, 2020 ), and human HF MSCs ( Ou et al, 2020 ). Though these cell-based therapies have shown promising results they have yet to achieve the desired results in hair growth.…”

Mesenchymal Stromal Cell-Conditioned Medium for Skin Diseases: A Systematic Review

“…Ten studies evaluated the effect of MSC-CM on hair growth at the preclinical level (Park et al, 2010;Won et al, 2010Won et al, , 2015Dong et al, 2014;Shim, 2015;Choi et al, 2019;Gunawardena et al, 2019a;Ou et al, 2020;Xiao et al, 2020; Table 7). MSCs were isolated mainly from human hair follicles (Won et al, 2010;Won et al, 2015;Gunawardena et al, 2019a;Ou et al, 2020) (40%, 4/10) and human adipose tissue (Park et al, 2010;Choi et al, 2019;Xiao et al, 2020) (30%, 3/10). Other tissues used were human amniotic fluid , human deciduous teeth (Gunawardena et al, 2019a), human dermal cells (Shim, 2015), and murine bone marrow (Dong et al, 2014).…”

“…All studies employed murine models. Mesenchymal stromal cell-CM was used subcutaneously (Park et al, 2010;Won et al, 2015;Choi et al, 2019;Gunawardena et al, 2019a;Xiao et al, 2020) (50%, 5/10) or intradermally (Dong et al, 2014) injected or topically applied (Won et al, 2010;Shim, 2015;Ou et al, 2020) (40%, 4/10). MSC-CM was tested on 86 animals with shaved regions.…”

Hair Follicle Grafting Therapy Promotes Re-Emergence of Critical Skin Components in Chronic Nonhealing Wounds

“…The advantage of using hair follicle grafts over epidermal grafts or cultured keratinocytes is also established in the field, wherein hair follicle grafting is a more effective and technically easier method to treat chronic wounds (Nuutila, 2021;Yang et al, 2015;Weyandt et al, 2009). Additionally, these hair follicle units contain multiple types of stem cells including both epithelial and mesenchymal stem cells, neuronal progenitors as well as muscle cell progenitors [ (Tiede et al, 2007), (Gentile et al, 2017), (Ou et al, 2020), (Mignone et al, 2007), (Sieber-Blum et al, 2004, (Tohgi et al, 2017), (Xu et al, 2013)]. Interestingly, MSCs have an additional value given their anti-inflammatory capacity [ (Wang et al, 2016), (Prockop and Youn Oh, 2012), (Chahal et al, 2019), (Pers et al, J o u r n a l P r e -p r o o f 2018), (González et al, 2009), (Ghoryani et al, 2019)].…”

“…The advantage of using HF grafts over epidermal grafts or cultured keratinocytes is also established in the field, in which HF grafting is a more effective and technically easier method to treat chronic wounds ( Nuutila, 2021 , Weyandt et al, 2009 , Yang et al, 2015 ). In addition, these HF units contain multiple types of SCs, including both epithelial SCs and MSCs, neuronal progenitors, as well as muscle cell progenitors ( Gentile et al., 2017 ; Mignone et al., 2007 ; Ou et al., 2020 ; Sieber-Blum et al., 2004 ; Tiede et al., 2007 ; Tohgi et al., 2017 ; Xu et al., 2013 ). Interestingly, MSCs have an additional value given their anti-inflammatory capacity ( Chahal et al., 2019 ; Ghoryani et al., 2019 ; González et al., 2009 ; Pers et al., 2018 ; Prockop and Oh, 2012 ; Wang et al., 2016 ).…”