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From Hair to the Brain: The Short-Term Therapeutic Potential of Human Hair Follicle-Derived Stem Cells and Their Conditioned Medium in a Rat Model of Stroke

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Abstract

The short-term therapeutic impacts of stem cells and their derivatives were frequently reported in preclinical investigations of ischemic stroke (IS); however, several drawbacks including accessibility, abundancy, and ethical concerns limited their clinical application. We describe here for the first time the therapeutic potential of human hair follicle-derived stem cells (hHFSCs) and their conditioned medium (CM) in a rat model of IS. Furthermore, we hypothesized that a combination of cell therapy with repeated CM administration might enhance the restorative efficiency of this approach compared to each treatment alone. Middle cerebral artery occlusion was performed for 30 min to induce IS. Immediately after reperfusion, hHFSCs were transplanted through the intra-arterial route and/or hHFSC-CM administered intranasally. The neurological outcomes, short-term spatial working memory, and infarct size were evaluated. Furthermore, relative expression of seven target genes in three categories of neuronal markers, synaptic markers, and angiogenic markers was assessed. The hHFSCs and hHFSC-CM treatments improved neurological impairments and reduced infarct size in the IS rats. Moreover, molecular data elucidated that IS was accompanied by attenuation in the expression of neuronal and synaptic markers in the evaluated brain regions and the interventions rescued these expression changes. Although there was no considerable difference between hHFSCs and hHFSC-CM treatments in the improvement of neurological function and decrement of infarct size, combination therapy was more effective to reduce infarction and elevation of target gene expression especially in the hippocampus. These findings highlight the curative potential of hHFSCs and their CM in a rat model of IS.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding authors on reasonable request.

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Funding

This study was financially supported by Shiraz University of Medical Sciences (Grant number: 22014) and Iran National Science Foundation (INSF, Grant number: 99008590).

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Author notes

  1. Saeideh Karimi-Haghighi and Sareh Pandamooz contributed equally to this work.

Authors and Affiliations

  1. Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Saeideh Karimi-Haghighi, Etrat Hooshmandi, Mahnaz Bayat, Maryam Owjfard, Seyedeh Shaghayegh Zafarmand, Seyedeh Maryam Mousavi, Vida Eraghi, Nima Fadakar, Abbas Rahimi Jaberi, Mohammad Saied Salehi & Afshin Borhani-Haghighi

  2. Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Sareh Pandamooz, Anahid Safari, Mehdi Dianatpour & Mandana Mostaghel

  3. Institute for Molecular and Cellular Anatomy, University of Regensburg, Regensburg, Germany

    Benjamin Jurek

  4. North Research Center of Pasteur Institute, Amol, Iran

    Sadegh Fattahi

  5. Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Negar Azarpira

  6. Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

    Nahid Jashire Nezhad

  7. Department of Neurology, John Hunter Hospital, Newcastle, Australia

    Carlos Garcia-Esperon, Neil Spratt, Christopher Levi & Afshin Borhani-Haghighi

  8. Hunter Medical Research Institute and the University of Newcastle, Newcastle, Australia

    Carlos Garcia-Esperon, Neil Spratt, Christopher Levi & Afshin Borhani-Haghighi

Authors
  1. Saeideh Karimi-Haghighi
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  2. Sareh Pandamooz
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Contributions

All authors contributed to the study conception and design. The study was designed by Sareh Pandamooz, Mohammad Saied Salehi, and Afshin Borhani-Haghighi. Data collection and analysis were performed by Saeideh Karimi-Haghighi, Sadegh Fattahi, Etrat Hooshmandi, Mahnaz Bayat, Maryam Owjfard, Seyedeh Shaghayegh Zafarmand, Mandana Mostaghel, Seyedeh Maryam Mousavi, Nahid Jashire Nezhad, and Vida Eraghi. Material preparation was performed by Anahid Safari, Negar Azarpira, Mehdi Dianatpour, Nima Fadakar, and Abbas Rahimi Jaberi. The manuscript was critically revised by Benjamin Jurek, Carlos Garcia-Esperon, Neil Spratt, and Christopher Levi. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Mohammad Saied Salehi or Afshin Borhani-Haghighi.

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Animal procedures were conducted in accordance with the Guide for the Care and Use of Laboratory Animals (National Institutes of Health Publication, 8th edition, revised 2011). The study was approved by Shiraz University of Medical Sciences, Shiraz, Iran (IR.SUMS.REC.1399.1150). Complying with ARRIVE guidelines[11], all attempts were conducted to decrease animal suffering and minimize the number of animals.

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Karimi-Haghighi, S., Pandamooz, S., Jurek, B. et al. From Hair to the Brain: The Short-Term Therapeutic Potential of Human Hair Follicle-Derived Stem Cells and Their Conditioned Medium in a Rat Model of Stroke. Mol Neurobiol 60, 2587–2601 (2023). https://doi.org/10.1007/s12035-023-03223-z

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