Identification and characterization of stem cell secretome-based recombinant proteins for wound healing applications
Stem cells have been introduced as a promising therapy for acute and chronic wounds, including burn injuries. The effects of stem cell-based wound therapies are believed to result from the secreted bioactive molecules produced by stem cells. Therefore, treatments using stem cell-derived conditioned...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2022.954682/full |
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| author | Ji Hyun Kim Denethia S. Green Young Min Ju Mollie Harrison J. William Vaughan Anthony Atala Sang Jin Lee John D. Jackson Cory Nykiforuk James J. Yoo |
| author_facet | Ji Hyun Kim Denethia S. Green Young Min Ju Mollie Harrison J. William Vaughan Anthony Atala Sang Jin Lee John D. Jackson Cory Nykiforuk James J. Yoo |
| author_sort | Ji Hyun Kim |
| collection | DOAJ |
| description | Stem cells have been introduced as a promising therapy for acute and chronic wounds, including burn injuries. The effects of stem cell-based wound therapies are believed to result from the secreted bioactive molecules produced by stem cells. Therefore, treatments using stem cell-derived conditioned medium (CM) (referred to as secretome) have been proposed as an alternative option for wound care. However, safety and regulatory concerns exist due to the uncharacterized biochemical content and variability across different batches of CM samples. This study presents an alternative treatment strategy to mitigate these concerns by using fully characterized recombinant proteins identified by the CM analysis to promote pro-regenerative healing. This study analyzed the secretome profile generated from human placental stem cell (hPSC) cultures and identified nine predominantly expressed proteins (ANG-1, FGF-7, Follistatin, HGF, IL-6, Insulin, TGFβ-1, uPAR, and VEGF) that are known to contribute to wound healing and angiogenesis. These proteins, referred to as s (CMFs), were used in combination to test the effects on human dermal fibroblasts (HDFs). Our results showed that CMF treatment increased the HDF growth and accelerated cell migration and wound closure, similar to stem cell and CM treatments. In addition, the CMF treatment promoted angiogenesis by enhancing new vessel formation. These findings suggest that the defined CMF identified by the CM proteomic analysis could be an effective therapeutic solution for wound healing applications. Our strategy eliminates the regulatory concerns present with stem cell-derived secretomes and could be developed as an off-the-shelf product for immediate wound care and accelerating healing. |
| first_indexed | 2024-12-12T00:01:07Z |
| format | Article |
| id | doaj.art-dd0ef0eb233d4825a98088615f7172b8 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-12T00:01:07Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-dd0ef0eb233d4825a98088615f7172b82022-12-22T00:45:14ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-07-011010.3389/fbioe.2022.954682954682Identification and characterization of stem cell secretome-based recombinant proteins for wound healing applicationsJi Hyun Kim0Denethia S. Green1Young Min Ju2Mollie Harrison3J. William Vaughan4Anthony Atala5Sang Jin Lee6John D. Jackson7Cory Nykiforuk8James J. Yoo9Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesWake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesWake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesWake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesWake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesWake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesWake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesWake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesEmergent BioSolutions, Winnipeg, MB, CanadaWake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesStem cells have been introduced as a promising therapy for acute and chronic wounds, including burn injuries. The effects of stem cell-based wound therapies are believed to result from the secreted bioactive molecules produced by stem cells. Therefore, treatments using stem cell-derived conditioned medium (CM) (referred to as secretome) have been proposed as an alternative option for wound care. However, safety and regulatory concerns exist due to the uncharacterized biochemical content and variability across different batches of CM samples. This study presents an alternative treatment strategy to mitigate these concerns by using fully characterized recombinant proteins identified by the CM analysis to promote pro-regenerative healing. This study analyzed the secretome profile generated from human placental stem cell (hPSC) cultures and identified nine predominantly expressed proteins (ANG-1, FGF-7, Follistatin, HGF, IL-6, Insulin, TGFβ-1, uPAR, and VEGF) that are known to contribute to wound healing and angiogenesis. These proteins, referred to as s (CMFs), were used in combination to test the effects on human dermal fibroblasts (HDFs). Our results showed that CMF treatment increased the HDF growth and accelerated cell migration and wound closure, similar to stem cell and CM treatments. In addition, the CMF treatment promoted angiogenesis by enhancing new vessel formation. These findings suggest that the defined CMF identified by the CM proteomic analysis could be an effective therapeutic solution for wound healing applications. Our strategy eliminates the regulatory concerns present with stem cell-derived secretomes and could be developed as an off-the-shelf product for immediate wound care and accelerating healing.https://www.frontiersin.org/articles/10.3389/fbioe.2022.954682/fullstem cell secretomeconditioned mediumrecombinant proteinswound healingskin regenerationtissue engineering and regenerative medicine |
| spellingShingle | Ji Hyun Kim Denethia S. Green Young Min Ju Mollie Harrison J. William Vaughan Anthony Atala Sang Jin Lee John D. Jackson Cory Nykiforuk James J. Yoo Identification and characterization of stem cell secretome-based recombinant proteins for wound healing applications Frontiers in Bioengineering and Biotechnology stem cell secretome conditioned medium recombinant proteins wound healing skin regeneration tissue engineering and regenerative medicine |
| title | Identification and characterization of stem cell secretome-based recombinant proteins for wound healing applications |
| title_full | Identification and characterization of stem cell secretome-based recombinant proteins for wound healing applications |
| title_fullStr | Identification and characterization of stem cell secretome-based recombinant proteins for wound healing applications |
| title_full_unstemmed | Identification and characterization of stem cell secretome-based recombinant proteins for wound healing applications |
| title_short | Identification and characterization of stem cell secretome-based recombinant proteins for wound healing applications |
| title_sort | identification and characterization of stem cell secretome based recombinant proteins for wound healing applications |
| topic | stem cell secretome conditioned medium recombinant proteins wound healing skin regeneration tissue engineering and regenerative medicine |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2022.954682/full |
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