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Stem Cell Applications in Lysosomal Storage Disorders: Progress and Ongoing Challenges

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Cell Biology and Translational Medicine, Volume 14

Part of the book series: Advances in Experimental Medicine and Biology ((CBTMED,volume 1347))

Abstract

Lysosomal storage disorders (LSDs) are rare inborn errors of metabolism caused by defects in lysosomal function. These diseases are characterized by accumulation of completely or partially degraded substrates in the lysosomes leading to cellular dysfunction of the affected cells. Currently, enzyme replacement therapies (ERTs), treatments directed at substrate reduction (SRT), and hematopoietic stem cell (HSC) transplantation are the only treatment options for LSDs, and the effects of these treatments depend strongly on the type of LSD and the time of initiation of treatment. However, some of the LSDs still lack a durable and curative treatment. Therefore, a variety of novel treatments for LSD patients has been developed in the past few years. However, despite significant progress, the efficacy of some of these treatments remains limited because these therapies are often initiated after irreversible organ damage has occurred.

Here, we provide an overview of the known effects of LSDs on stem cell function, as well as a synopsis of available stem cell-based cell and gene therapies that have been/are being developed for the treatment of LSDs. We discuss the advantages and disadvantages of use of hematopoietic stem cell (HSC), mesenchymal stem cell (MSC), and induced pluripotent stem cell (iPSC)-related (gene) therapies. An overview of current research data indicates that when stem cell and/or gene therapy applications are used in combination with existing therapies such as ERT, SRT, and chaperone therapies, promising results can be achieved, showing that these treatments may result in alleviation of existing symptoms and/or prevention of progression of the disease. All together, these studies offer some insight in LSD stem cell biology and provide a hopeful perspective for the use of stem cells. Further development and improvement of these stem cell (gene) combination therapies may greatly improve the current treatment options and outcomes of patients with a LSD.

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Abbreviations

AAV:

Adeno-associated vectors

ARSA:

Arylsulfatase A

ASM:

Acid sphingomyelinase

BBB:

Brain-blood barrier

BM:

Bone marrow

BMT:

Bone marrow transplantation

CNS:

Central nervous system

ER:

Endoplasmic reticulum

ERT:

Enzyme replacement therapy

GAG:

Glycosaminoglycan

GD:

Gaucher disease

GSD:

Glycogen storage disease

GUSB:

Beta-glucuronidase

GvHD:

Graft-versus-host disease

HSCT:

Hematopoietic stem cell transplantation

iPSCs:

Induced pluripotent stem cells

LSD:

Lysosomal storage disease/disorder

LV:

Lentiviral vectors

MASCs:

Multipotent adult stem cells

M-CSF:

Macrophage colony-stimulating factor

MLD:

Metachromatic leukodystrophy

MPS:

Mucopolysaccharidosis

MPS-IH:

Hurler’s disease

MSC:

Mesenchymal stem cell

NSC:

Neural stem cells

PB:

Peripheral blood

PCT:

Pharmacological chaperone therapy

SIN:

Self-inactivating

SRT:

Substrate reduction therapy

UCB:

Umbilical cord blood

UCBT:

Umbilical cord blood transplantation

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Acknowledgments

This study was supported by a grant from the Turkish Ministry of Development, PediSTEM nr. 2006-K120640, and the Scientific and Technological Research Council of Turkey (TUBİTAK), project nr. 219S675.

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

The authors declare that this article does not contain any studies with human participants or animals.

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Author notes

  1. Authors Sevil Köse and Fatima Aerts-Kaya have equally contributed to this chapter.

Authors and Affiliations

  1. Department of Medical Biology, Faculty of Medicine, Atilim University, Ankara, Turkey

    Sevil Köse

  2. Department of Stem Cell Sciences, Hacettepe University Graduate School of Health Sciences, Ankara, Turkey

    Fatima Aerts-Kaya

  3. Hacettepe University Center for Stem Cell Research and Development (PEDI-STEM), Ankara, Turkey

    Fatima Aerts-Kaya

  4. Hacettepe University Faculty of Medicine, Department of Pediatrics, Division of Hematology, Hacettepe University Center for Stem Cell Research and Development (PEDI-STEM), Ankara, Turkey

    Duygu Uçkan Çetinkaya

  5. Department of Stem Cell Sciences, Hacettepe University Graduate School of Health Sciences, Ankara, Turkey

    Duygu Uçkan Çetinkaya

  6. Department of Histology and Embryology, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Petek Korkusuz

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  1. Sevil Köse
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  1. (emeritus) Ottawa Hospital Research Institute, Ottawa, ON, Canada

    Kursad Turksen

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Köse, S., Aerts-Kaya, F., Uçkan Çetinkaya, D., Korkusuz, P. (2021). Stem Cell Applications in Lysosomal Storage Disorders: Progress and Ongoing Challenges. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 14. Advances in Experimental Medicine and Biology(), vol 1347. Springer, Cham. https://doi.org/10.1007/5584_2021_639

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