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Review Article


Preclinical studies of conditioned medium of hypoxic-preconditioned mesenchymal stem cell/hypMSC-CM for ischemic stroke: A systematic review

Ratih Rinendyaputri, Uly Alfi Nikmah, Novaria Sari Dewi Panjaitan, Putri Reno Intan, Jiro Hasegawa Situmorang, Hasta Handayani Idrus, Rilianawati Rilianawati, Wireni Ayuningtyas, Rachmawati Noverina, Fathul Huda, Ahmad Faried.


Abstract
The current treatment for ischemic stroke, tissue plasminogen activator (tPA), is limited by a narrow therapeutic window, necessitating the development of adjuvant therapies. Hypoxic preconditioning is a strategy to improve the therapeutic potential of mesenchymal stem cells. The secretome of hypoxic mesenchymal stem cell-conditioned medium (hypMSC-CM) is an effective therapy for vascular lesions like stroke, as it promotes angiogenesis, neurogenesis, and neuroprotection. This systematic review aimed to assess the efficacy of hypMSC-CM in in vivo and in vitro stroke models to inform future clinical trials on stroke treatment. A systematic search was conducted for studies on hypMSC-CM in ischemic stroke models using the PubMed, Scopus, and Google Scholar databases up to December 2024. A total of 91 articles were identified, of which six met the eligibility criteria. Data were extracted from six studies (three in vivo and three in vitro), and their therapeutic outcomes are summarized in tables. All included studies consistently demonstrated beneficial effects of hypMSC-CM, with findings of reduced infarct volume, improved neurological function, and the promotion of neurogenesis and angiogenesis. This systematic review suggests that hypMSC-CM enhances neurogenesis and neuroprotection in the brain. However, high-quality preclinical studies and clinical trials are needed to support the therapeutic benefits of hypMSC-CM for ischemic stroke, especially as an adjuvant to standard tPA therapy.

Key words: Conditioned medium of hypoxic-preconditioned mesenchymal stem cell/hypMSC-CM; Stroke ischemic; Neuroprotection; Angiogenesis; Mesenchymal stem cell/MSC.


 
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How to Cite this Article
Pubmed Style

Rinendyaputri R, Nikmah UA, Panjaitan NSD, Intan PR, Situmorang JH, Idrus HH, Rilianawati R, Ayuningtyas W, Noverina R, Huda F, Faried A. Preclinical studies of conditioned medium of hypoxic-preconditioned mesenchymal stem cell/hypMSC-CM for ischemic stroke: A systematic review. Open Vet. J.. 2026; 16(1): 41-55. doi:10.5455/OVJ.2026.v16.i1.4

Web Style

Rinendyaputri R, Nikmah UA, Panjaitan NSD, Intan PR, Situmorang JH, Idrus HH, Rilianawati R, Ayuningtyas W, Noverina R, Huda F, Faried A. Preclinical studies of conditioned medium of hypoxic-preconditioned mesenchymal stem cell/hypMSC-CM for ischemic stroke: A systematic review. https://www.openveterinaryjournal.com/?mno=279773 [Access: January 31, 2026]. doi:10.5455/OVJ.2026.v16.i1.4

AMA (American Medical Association) Style

Rinendyaputri R, Nikmah UA, Panjaitan NSD, Intan PR, Situmorang JH, Idrus HH, Rilianawati R, Ayuningtyas W, Noverina R, Huda F, Faried A. Preclinical studies of conditioned medium of hypoxic-preconditioned mesenchymal stem cell/hypMSC-CM for ischemic stroke: A systematic review. Open Vet. J.. 2026; 16(1): 41-55. doi:10.5455/OVJ.2026.v16.i1.4


Vancouver/ICMJE Style

Rinendyaputri R, Nikmah UA, Panjaitan NSD, Intan PR, Situmorang JH, Idrus HH, Rilianawati R, Ayuningtyas W, Noverina R, Huda F, Faried A. Preclinical studies of conditioned medium of hypoxic-preconditioned mesenchymal stem cell/hypMSC-CM for ischemic stroke: A systematic review. Open Vet. J.. (2026), [cited January 31, 2026]; 16(1): 41-55. doi:10.5455/OVJ.2026.v16.i1.4


Harvard Style

Rinendyaputri, R., Nikmah, . U. A., Panjaitan, . N. S. D., Intan, . P. R., Situmorang, . J. H., Idrus, . H. H., Rilianawati, . R., Ayuningtyas, . W., Noverina, . R., Huda, . F. & Faried, . A. (2026) Preclinical studies of conditioned medium of hypoxic-preconditioned mesenchymal stem cell/hypMSC-CM for ischemic stroke: A systematic review. Open Vet. J., 16 (1), 41-55. doi:10.5455/OVJ.2026.v16.i1.4


Turabian Style

Rinendyaputri, Ratih, Uly Alfi Nikmah, Novaria Sari Dewi Panjaitan, Putri Reno Intan, Jiro Hasegawa Situmorang, Hasta Handayani Idrus, Rilianawati Rilianawati, Wireni Ayuningtyas, Rachmawati Noverina, Fathul Huda, and Ahmad Faried. 2026. Preclinical studies of conditioned medium of hypoxic-preconditioned mesenchymal stem cell/hypMSC-CM for ischemic stroke: A systematic review. Open Veterinary Journal, 16 (1), 41-55. doi:10.5455/OVJ.2026.v16.i1.4


Chicago Style

Rinendyaputri, Ratih, Uly Alfi Nikmah, Novaria Sari Dewi Panjaitan, Putri Reno Intan, Jiro Hasegawa Situmorang, Hasta Handayani Idrus, Rilianawati Rilianawati, Wireni Ayuningtyas, Rachmawati Noverina, Fathul Huda, and Ahmad Faried. "Preclinical studies of conditioned medium of hypoxic-preconditioned mesenchymal stem cell/hypMSC-CM for ischemic stroke: A systematic review." Open Veterinary Journal 16 (2026), 41-55. doi:10.5455/OVJ.2026.v16.i1.4


MLA (The Modern Language Association) Style

Rinendyaputri, Ratih, Uly Alfi Nikmah, Novaria Sari Dewi Panjaitan, Putri Reno Intan, Jiro Hasegawa Situmorang, Hasta Handayani Idrus, Rilianawati Rilianawati, Wireni Ayuningtyas, Rachmawati Noverina, Fathul Huda, and Ahmad Faried. "Preclinical studies of conditioned medium of hypoxic-preconditioned mesenchymal stem cell/hypMSC-CM for ischemic stroke: A systematic review." Open Veterinary Journal 16.1 (2026), 41-55. Print. doi:10.5455/OVJ.2026.v16.i1.4


APA (American Psychological Association) Style

Rinendyaputri, R., Nikmah, . U. A., Panjaitan, . N. S. D., Intan, . P. R., Situmorang, . J. H., Idrus, . H. H., Rilianawati, . R., Ayuningtyas, . W., Noverina, . R., Huda, . F. & Faried, . A. (2026) Preclinical studies of conditioned medium of hypoxic-preconditioned mesenchymal stem cell/hypMSC-CM for ischemic stroke: A systematic review. Open Veterinary Journal, 16 (1), 41-55. doi:10.5455/OVJ.2026.v16.i1.4


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