Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Reviews in the Neurosciences

Editor-in-Chief: Huston, Joseph P.

Editorial Board: Topic, Bianca / Adeli, Hojjat / Buzsaki, Gyorgy / Crawley, Jacqueline / Crow, Tim / Gold, Paul / Holsboer, Florian / Korth, Carsten / Lubec, Gert / McEwen, Bruce / Pan, Weihong / Pletnikov, Mikhail / Robbins, Trevor / Schnitzler, Alfons / Stevens, Charles / Steward, Oswald / Trojanowski, John

8 Issues per year


IMPACT FACTOR 2017: 2.590
5-year IMPACT FACTOR: 3.078

CiteScore 2017: 2.81

SCImago Journal Rank (SJR) 2017: 0.980
Source Normalized Impact per Paper (SNIP) 2017: 0.804

Online
ISSN
2191-0200
See all formats and pricing
More options …
Volume 29, Issue 3

Issues

Regenerative potential of secretome from dental stem cells: a systematic review of preclinical studies

Suleiman Alhaji Muhammad
  • Institute of Bioscience, Universiti Putra, Serdang, Selangor, Malaysia
  • Department of Biochemistry, Usmanu Danfodiyo University, Sokoto, Nigeria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Norshariza Nordin
  • Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra, Serdang, Selangor, Malaysia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Sharida Fakurazi
  • Corresponding author
  • Institute of Bioscience and Pharmacology Unit, Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2017-12-08 | DOI: https://doi.org/10.1515/revneuro-2017-0069

Abstract

Injury to tissues is a major clinical challenge due to the limited regenerative capacity of endogenous cells. Stem cell therapy is evolving rapidly as an alternative for tissue regeneration. However, increasing evidence suggests that the regenerative ability of stem cells is mainly mediated by paracrine actions of secretome that are generally secreted by the cells. We aimed to systematically evaluate the efficacy of dental stem cell (DSC)-conditioned medium in in vivo animal models of various tissue defects. A total of 15 eligible studies was included by searching Pubmed, Scopus and Medline databases up to August 2017. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool. Of 15 studies, seven reported the therapeutic benefit of the conditioned medium on neurological diseases and three reported on joint/bone-related defects. Two interventions were on liver diseases, whereas the remaining three addressed myocardial infarction and reperfusion, lung injury and diabetes. Nine studies were performed using mouse models and the remaining six studies used rat models. The methodological quality of the studies was low, as most of the key elements required in reports of preclinical studies were not reported. The findings of this review suggested that conditioned medium from DSCs improved tissue regeneration and functional recovery. This current review strengthens the therapeutic benefit of cell-free product for tissue repair in animal models. A well-planned study utilizing validated outcome measures and long-term safety studies are required for possible translation to clinical trials.

Keywords: conditioned medium; dental stem cells; secretome; tissue defect; tissue regeneration

References

  • Agacayak, S., Gulsun, B., Ucan, M.C., Karaoz, E., and Nergiz, Y. (2012). Effects of mesenchymal stem cells in critical size bone defect. Eur. Rev. Med. Pharmacol. Sci. 16, 679–686.PubMedGoogle Scholar

  • Ahmed, N.E.M.B., Murakami, M., Hirose, Y., and Nakashima, M. (2016). Therapeutic potential of dental pulp stem cell secretome for Alzheimer’s disease treatment: an in vitro study. Stem Cells Int. 2016, 11.Google Scholar

  • Akyurekli, C., Le, Y., Richardson, R.B., Fergusson, D., Tay, J., and Allan, D.S. (2015). A systematic review of preclinical studies on the therapeutic potential of mesenchymal stromal cell-derived microvesicles. Stem Cell Rev. Rep. 11, 150–160.CrossrefGoogle Scholar

  • Babaei, P., Soltani Tehrani, B., and Alizadeh, A. (2012). Transplanted bone marrow mesenchymal stem cells improve memory in rat models of Alzheimer’s disease. Stem Cells Int. 2012, 369417.PubMedGoogle Scholar

  • Baraniak, P.R. and McDevitt, T.C. (2010). Stem cell paracrine actions and tissue regeneration. Regen. Med. 5, 121–143.PubMedCrossrefGoogle Scholar

  • Bernardo, M.E. and Fibbe, W.E. (2012). Safety and efficacy of mesenchymal stromal cell therapy in autoimmune disorders. Ann. NY Acad. Sci. 1266, 107–117.CrossrefGoogle Scholar

  • Camussi, G., Deregibus, M.C., and Cantaluppi, V. (2013). Role of stem-cell-derived microvesicles in the paracrine action of stem cells. Biochem. Soc. Trans. 41, 283–287.PubMedCrossrefGoogle Scholar

  • Cho, H.H., Jang, S., Lee, S.C., Jeong, H.S., Park, J.S., Han, J.Y., Lee, K.H., and Cho, Y.B. (2010). Effect of neural-induced mesenchymal stem cells and platelet-rich plasma on facial nerve regeneration in an acute nerve injury model. Laryngoscope 120, 907–913.Google Scholar

  • Curley, G.F., Hayes, M., Ansari, B., Shaw, G., Ryan, A., Barry, F., O‘brien, T., O’Toole, D., and Laffey, J.G. (2012). Mesenchymal stem cells enhance recovery and repair following ventilator-induced lung injury in the rat. Thorax 67, 496–501.PubMedCrossrefGoogle Scholar

  • Fang, C., Yang, Y., Wang, Q., Yao, Y., Zhang, X., and He, X. (2013). Intraventricular injection of human dental pulp stem cells improves hypoxic-ischemic brain damage in neonatal rats. PloS One 8, e66748.PubMedCrossrefGoogle Scholar

  • Fujio, M., Xing, Z., Sharabi, N., Xue, Y., Yamamoto, A., Hibi, H., Ueda, M., Fristad, I., and Mustafa, K. (2017). Conditioned media from hypoxic-cultured human dental pulp cells promotes bone healing during distraction osteogenesis. J. Tissue Eng. Regen. Med. 11, 2116–2126.PubMedCrossrefGoogle Scholar

  • Glenn, J.D. and Whartenby, K.A. (2014). Mesenchymal stem cells: emerging mechanisms of immunomodulation and therapy. World J. Stem Cells 6, 526.CrossrefPubMedGoogle Scholar

  • Henderson, V.C., Kimmelman, J., Fergusson, D., Grimshaw, J.M., and Hackam, D.G. (2013). Threats to validity in the design and conduct of preclinical efficacy studies: a systematic review of guidelines for in vivo animal experiments. PLoS Med. 10, e1001489.CrossrefGoogle Scholar

  • Herberts., C.A., Kwa, M. S., and Hermsen, H.P. (2011). Risk factors in the development of stem cell therapy. J. Transl. Med. 9, 29.CrossrefPubMedGoogle Scholar

  • Hirata, M., Ishigami, M., Matsushita, Y., Ito, T., Hattori, H., Hibi, H., Goto, H., Ueda, M., and Yamamoto, A. (2016). Multifaceted therapeutic benefits of factors derived from dental pulp stem cells for mouse liver fibrosis. Stem Cells Transl. Med. 5, 1416–1424.PubMedCrossrefGoogle Scholar

  • Hooijmans, C.R., Rovers, M.M., de Vries, R.B., Leenaars, M., Ritskes-Hoitinga, M., and Langendam, M.W. (2014). SYRCLE’s risk of bias tool for animal studies. BMC Med. Res. Methodol. 14, 43.PubMedCrossrefGoogle Scholar

  • Huang, S. and Fu, X. (2010). Naturally derived materials-based cell and drug delivery systems in skin regeneration. J. Control. Release 142, 149–159.PubMedCrossrefGoogle Scholar

  • Huang, G. J., Gronthos, S., and Shi, S. (2009). Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J. Dent. Res. 88, 792–806.PubMedCrossrefGoogle Scholar

  • Inoue, T., Sugiyama, M., Hattori, H., Wakita, H., Wakabayashi, T., and Ueda, M. (2013). Stem cells from human exfoliated deciduous tooth-derived conditioned medium enhance recovery of focal cerebral ischemia in rats. Tissue Eng. Part A 19, 24–29.CrossrefPubMedGoogle Scholar

  • Ishikawa, J., Takahashi, N., Matsumoto, T., Yoshioka, Y., Yamamoto, N., Nishikawa, M., Hibi, H., Ishiguro, N., Ueda, M., Furukawa, K., et al. (2016). Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental rheumatoid arthritis. Bone 83, 210–219.CrossrefPubMedGoogle Scholar

  • Izumoto-Akita, T., Tsunekawa, S., Yamamoto, A., Uenishi, E., Ishikawa, K., Ogata, H., Iida, A., Ikeniwa, M., Hosokawa, K., Niwa, Y., et al. (2015). Secreted factors from dental pulp stem cells improve glucose intolerance in streptozotocin-induced diabetic mice by increasing pancreatic β-cell function. BMJ Open Diab. Res. Care 3, e000128.CrossrefGoogle Scholar

  • Kano, F., Matsubara, K., Ueda, M., Hibi, H., and Yamamoto, A. (2017). Secreted ectodomain of sialic acid-binding Ig-like lectin-9 and MCP-1 synergistically regenerate transected rat peripheral nerves by altering macrophage polarity. Stem Cells 35, 641–653.CrossrefPubMedGoogle Scholar

  • Kim, I.K., Kim, S.H., Choi, S.M., Youn, B.S., and Kim, H.S. (2016). Extracellular vesicles as drug delivery vehicles for rheumatoid arthritis. Curr. Stem Cell Res. Ther. 11, 329–342.PubMedCrossrefGoogle Scholar

  • Koh, S.H., Kim, K.S., Choi, M.R., Jung, K.H., Park, K.S., Chai, Y.G., Roh, W., Hwang, S.J., Ko, H.J., Huh, Y.M., et al. (2008). Implantation of human umbilical cord-derived mesenchymal stem cells as a neuroprotective therapy for ischemic stroke in rats. Brain Res. 1229, 233–248.CrossrefPubMedGoogle Scholar

  • Kumasaka, A., Kanazawa, K., Ohke, H., Miura, I., and Miura, Y. (2017). Post-ischemic intravenous administration of allogeneic dental pulp-derived neurosphere cells ameliorated outcomes of severe forebrain ischemia in rats. Neurocrit. Care 26, 133–142.CrossrefPubMedGoogle Scholar

  • Kusindarta, D.L., Wihadmadyatami, H., Fibrianto, Y.H., Nugroho, W.S., Susetya, H., Musana, D.K., Wijayanto, H., Prihatna, S.A., and Wahyuni, A.E.T.H. (2016). Human umbilical mesenchymal stem cells conditioned medium promote primary wound healing regeneration. Vet. World. 9, 605–610.CrossrefPubMedGoogle Scholar

  • Ledesma-Martínez, E., Mendoza-Núñez, V.M., and Santiago-Osorio, E. (2016). Mesenchymal stem cells derived from dental pulp: a review. Stem Cells Int. 2016, 12.Google Scholar

  • Levy, Y.S., Bahat-Stroomza, M., Barzilay, R., Burshtein, A., Bulvik, S., Barhum, Y., Panet, H., Melamed, E., and Offen, D. (2008). Regenerative effect of neural-induced human mesenchymal stromal cells in rat models of Parkinson’s disease. Cytotherapy 10, 340–352.CrossrefPubMedGoogle Scholar

  • Ma, H., Wu, Y., Zhang, W., Dai, Y., Li F., Xu, Y., Wang, Y., Tu, H., Li, W., and Zhang, X. (2013). The effect of mesenchymal stromal cells on doxorubicin-induced nephropathy in rats. Cytotherapy 15, 703–711.PubMedCrossrefGoogle Scholar

  • Matsubara, K., Matsushita, Y., Sakai, K., Kano, F., Kondo, M., Noda, M., Hashimoto, N., Imagama, S., Ishiguro, N., Suzumura, A., et al. (2015). Secreted ectodomain of sialic acid-binding Ig-like lectin-9 and monocyte chemoattractant protein-1 promote recovery after rat spinal cord injury by altering macrophage polarity. J. Neurosci. 35, 2452–2464.CrossrefPubMedGoogle Scholar

  • Matsushita, Y., Ishigami, M., Matsubara, K., Kondo, M., Wakayama, H., Goto, H., Ueda, M., and Yamamoto, A. (2017). Multifaceted therapeutic benefits of factors derived from stem cells from human exfoliated deciduous teeth for acute liver failure in rats. J. Tissue Eng. Regen. Med. 11, 1888–1896.PubMedCrossrefGoogle Scholar

  • Mita, T., Furukawa-Hibi, Y., Takeuchi, H., Hattori, H., Yamada, K., Hibi, H., Ueda, M., and Yamamoto, A. (2015). Conditioned medium from the stem cells of human dental pulp improves cognitive function in a mouse model of Alzheimer’s disease. Behav. Brain Res. 293, 189–197.CrossrefGoogle Scholar

  • Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., and Group, T.P. (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 6, e1000097.CrossrefPubMedGoogle Scholar

  • Morad, G., Kheiri, L., and Khojasteh, A. (2013). Dental pulp stem cells for in vivo bone regeneration: a systematic review of literature. Arch. Oral Biol. 58, 1818–1827.CrossrefPubMedGoogle Scholar

  • Nagata, M., Iwasaki, K., Akazawa, K., Komaki, M., Yokoyama, N., Izumi, Y., and Morita, I. (2017). Conditioned medium from periodontal ligament stem cells enhances periodontal regeneration. Tissue Eng. Part A 23, 367–377.CrossrefPubMedGoogle Scholar

  • Park, J.H., Kim, D.Y., Sung, I.Y., Choi, G.H., Jeon, M.H., Kim, K.K., and Jeon, S.R. (2012). Long-term results of spinal cord injury therapy using mesenchymal stem cells derived from bone marrow in humans. Neurosurgery 70, 1238–1247.PubMedCrossrefGoogle Scholar

  • Pawitan, J.A. (2014). Prospect of stem cell conditioned medium in regenerative medicine. BioMed. Res. Int. 2014, e965849.Google Scholar

  • Peng, W., Xing, Z., Yang, J., Wang, Y., Wang, W., and Huang, W. (2014). The efficacy of erythropoietin in treating experimental traumatic brain injury: a systematic review of controlled trials in animal models. J. Neurosurg. 121, 653–664.CrossrefPubMedGoogle Scholar

  • Pimentel-Coelho, P.M. and Mendez-Otero, R. (2010). Cell therapy for neonatal hypoxic-ischemic encephalopathy. Stem Cells Dev. 19, 299–310.CrossrefPubMedGoogle Scholar

  • Risbud, M. (2000). Tissue engineering: implications in the treatment of organ and tissue defects. Biogerontology 2, 117–125.Google Scholar

  • Sakai, K., Yamamoto, A., Matsubara, K., Nakamura, S., Naruse, M., Yamagata, M., Sakamoto, K., Tauchi, R., Wakao, N., Imagama, S., et al. (2012). Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms. J. Clin. Invest. 122, 80–90.PubMedGoogle Scholar

  • Sato, M., Uchida, K., Nakajima, H., Miyazaki, T., Guerrero, A.R., Watanabe, S., Roberts, S., and Baba, H. (2012). Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Res. Ther. 14, R31.PubMedCrossrefGoogle Scholar

  • Shimojima, C., Takeuchi, H., Jin, S., Parajuli, B., Hattori, H., Suzumura, A., Hibi, H., Ueda, M., and Yamamoto, A. (2016). Conditioned medium from the stem cells of human exfoliated deciduous teeth ameliorates experimental autoimmune encephalomyelitis. J. Immunol. 196, 4164–4171.PubMedCrossrefGoogle Scholar

  • Sugimura-Wakayama, Y., Katagiri, W., Osugi, M., Kawai, T., Ogata, K., Sakaguchi, K., and Hibi, H. (2015). Peripheral nerve regeneration by secretomes of stem cells from human exfoliated deciduous teeth. Stem Cells Dev. 24, 2687–2699.PubMedCrossrefGoogle Scholar

  • Timmers, L., Lim, S.K., Hoefer, I.E., Arslan, F., Lai, R.C., van Oorschot, A.A., Goumans, M.J., Strijder, C., Sze, S.K., Choo, A., et al. (2011). Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction. Stem Cell Res. 6, 206–214.PubMedCrossrefGoogle Scholar

  • Tsai, M.J., Tsai, S.K., Hu, B.R., Liou, D.Y., Huang, S.L., Huang, M.C., Huang, W.C., Cheng, H., and Huang, S.S. (2014). Recovery of neurological function of ischemic stroke by application of conditioned medium of bone marrow mesenchymal stem cells derived from normal and cerebral ischemia rats. J. Biomed. Sci. 21, 5.PubMedCrossrefGoogle Scholar

  • Tu, Y., Lineaweaver, W.C., Chen, Z., Hu, J., Mullins, F., and Zhang, F. (2017). Surgical decompression in the treatment of diabetic peripheral neuropathy: a systematic review and Meta-analysis. J. Reconstr. Microsurg. 33, 151–157.PubMedGoogle Scholar

  • Vishnubhatla, I., Corteling, R., Stevanato, L., Hicks, C., and Sinden, J. (2014). The development of stem cell-derived exosomes as a cell-free regenerative medicine. J. Circ. Biomark. 3, 2.CrossrefGoogle Scholar

  • Wakayama, H., Hashimoto, N., Matsushita, Y., Matsubara, K., Yamamoto, N., Hasegawa, Y., Ueda, M., and Yamamoto, A. (2015). Factors secreted from dental pulp stem cells show multifaceted benefits for treating acute lung injury in mice. Cytotherapy 17, 1119–1129.PubMedCrossrefGoogle Scholar

  • Wang, J., Ding, F., Gu, Y., Liu, J., and Gu, X. (2009). Bone marrow mesenchymal stem cells promote cell proliferation and neurotrophic function of Schwann cells in vitro and in vivo. Brain Res. 1262, 7–15.CrossrefPubMedGoogle Scholar

  • Wang, Z., Peng, W., Zhang, C., Sheng, C., Huang, W., Wang, Y., and Fan, R. (2015). Effects of stem cell transplantation on cognitive decline in animal models of Alzheimer’s disease: a systematic review and meta-analysis. Sci. Rep. 5, 12134.PubMedCrossrefGoogle Scholar

  • Xin, H., Li, Y., Liu, Z., Wang, X., Shang, X., Cui, Y., Zhang Z.G., and Chopp, M. (2013a). MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles. Stem Cells 31, 2737–2746.CrossrefGoogle Scholar

  • Xin, L.Z., Govindasamy, V., Musa, S., and Kasim, N.H. (2013b). Dental stem cells as an alternative source for cardiac regeneration. Med Hypotheses 81, 704–706.CrossrefGoogle Scholar

  • Yamagata, M., Yamamoto, A., Kako, E., Kaneko, N., Matsubara, K., Sakai, K., Sawamoto, K., and Ueda, M. (2013). Human dental pulp-derived stem cells protect against hypoxic-ischemic brain injury in neonatal mice. Stroke 44, 551–554.PubMedCrossrefGoogle Scholar

  • Yamaguchi, S., Shibata, R., Yamamoto, N., Nishikawa, M., Hibi, H., Tanigawa, T., Ueda, M., Murohara, T., and Yamamoto, A. (2015). Dental pulp-derived stem cell conditioned medium reduces cardiac injury following ischemia-reperfusion. Sci. Rep. 5, 16295.CrossrefPubMedGoogle Scholar

  • Yang, D., Wang, W., Li, L., Peng, Y., Chen, P., Huang, H., Guo, Y., Xia, X., Wang, Y., Wang, H., et al. (2013). The relative contribution of paracine effect versus direct differentiation on adipose-derived stem cell transplantation mediated cardiac repair. PLoS One 8, e59020.PubMedCrossrefGoogle Scholar

  • Yang, X., Zhu, T.Y., Wen, L.C., Cao, Y.P., Liu, C., Cui, Y.P., Meng, Z.C., and Liu, H. (2015). Intraarticular injection of allogenic mesenchymal stem cells has a protective role for the osteoarthritis. Chin. Med. J. 128, 2516.CrossrefGoogle Scholar

  • Yoshikawa, T., Mitsuno, H., Nonaka, I., Sen, Y., Kawanishi, K., Inada, Y., Takakura, Y., Okuchi, K., and Nonomura, A. (2008). Wound therapy by marrow mesenchymal cell transplantation. Plast. Reconstr. Surg. 121, 860–877.PubMedCrossrefGoogle Scholar

  • Zhang, W., Liu, X.C., Yang, L., Zhu, D.L., Zhang, Y.D., Chen, Y., and Zhang, H.Y. (2013). Wharton’s jelly-derived mesenchymal stem cells promote myocardial regeneration and cardiac repair after miniswine acute myocardial infarction. Coron. Artery Dis. 24, 549–558.PubMedCrossrefGoogle Scholar

  • Zirak Javanmard, M., Asgari, D., Karimipour, M., Atabaki, F., Farjah, G., and Niakani, A. (2015). Mesenchymal stem cells inhibit proteoglycan degeneration in a rat model of osteoarthritis. Gene Cell Tissue 2, e31011.Google Scholar

About the article

Received: 2017-08-15

Accepted: 2017-08-22

Published Online: 2017-12-08

Published in Print: 2018-03-28


Conflict of interest statement: The authors declare no potential conflicts of interest.


Citation Information: Reviews in the Neurosciences, Volume 29, Issue 3, Pages 321–332, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2017-0069.

Export Citation

©2018 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Suleiman Alhaji Muhammad, Norshariza Nordin, Muhammad Zulfadli Mehat, and Sharida Fakurazi
Cell and Tissue Research, 2018
[2]
Choung-Soo Kim
Korean Journal of Otorhinolaryngology-Head and Neck Surgery, 2018, Volume 61, Number 6, Page 275

Comments (0)

Please log in or register to comment.
Log in