The potential role of newborn stem cells in gene therapy

Image of ethnic female lab technician looking into a microscope.

The rapidly growing field of gene therapy involves the modification of a patient’s genetic information as a means of treating a genetic condition, thereby expanding or improving treatment options for human diseases. Through the process of editing, replacing, inhibiting, or adding a particular gene or genes, this emerging field aims to provide a treatment or cure for genetic conditions.

Newborn stem cells could serve as a source material for gene therapy

Newborn stem cells from umbilical cord blood and cord tissue may prove to be an ideal source of cells for gene therapy. Hematopoietic stem cells (HSCs), the same cells found in cord blood, are currently being investigated as a source of cells for gene therapy.¹ Mesenchymal stem cells (MSCs), the same cells found in cord tissue, are also being investigated as a source of cells for gene therapy based on their unique properties which may be enhanced through genetic engineering.^2,3

Because newborn stem cells from umbilical cord blood and cord tissue are easily collected at birth through non-invasive methods and can be cryogenically preserved for later use, they are an ideal source of cells for genetic manipulation outside the body (ex vivo).

Potential benefits of gene therapy using cord blood HSCs

Hematopoietic stem cells (HSCs) from umbilical cord blood are already well-established and widely used as a source of stem cells for stem cell transplants and are used to treat a number of blood and immune conditions, cancers, and metabolic disorders, many of which have a genetic basis.

Some transplants are deterred by the absence of HLA-matched donors and immunogenic complications from donor cells, such as graft-versus-host disease (GvHD), which can lead to post-transplant complications and increased mortality.⁴ Through ex vivo alteration of the causative gene in the patient’s own stem cells, which can then be used in an autologous transplant, gene therapy may prove to overcome these obstacles of immunogenicity and provide safer and potentially superior treatment options.⁵

Examples of therapeutic areas in which HSCs are currently being investigated for gene therapy include immune disorders such as severe combined immunodeficiency (SCID), hemoglobinopathies like sickle cell anemia, and metabolic conditions including Gaucher disease.6 While the HSCs in these trials are from adult sources, cord blood also contains the same type of stem cell utilized in these applications and thus could theoretically be used for these gene therapy treatments.

Potential benefits of gene therapy using MSCs

Mesenchymal stem cells (MSCs) like those found in cord tissue are known to exert anti-inflammatory properties, possess tumor-homing abilities, secrete bioactive molecules, and differentiate into multiple cell lineages.3 Current research aims to use gene therapy to enhance the innate characteristics of MSCs, which can then be used to target and repair damaged tissues.⁷

The use of genetically modified MSCs is being investigated to treat many different diseases such as solid-tumor cancers, cardiovascular disorders, and bone disease.^7,8,9

CBR®’s role in providing potential access to gene therapy

CBR’s Newborn Possibilities Program® provides no-cost cord blood and cord tissue processing plus 5 years of storage for families with a qualifying medical need. This program has preserved samples for over 11,000 babies, and our client families continue to benefit from proven and investigational therapies using their cryopreserved samples.¹⁰

In keeping abreast of the cutting-edge scientific developments in the field of gene therapy, the program’s eligibility has expanded to include babies with prenatal diagnoses of inherited conditions that can be treated with stem cell transplantation. Whereas patients with life-threatening genetic diseases were previously able to receive transplants only when cells from an HLA-matched donor were available, genetically-altered cells from these patients are now being researched for use in autologous curative treatments. It is important to note that gene therapy treatments using newborn stem cells are not yet available.

By providing access to newborn stem cell preservation, CBR gives families the potential opportunity to participate in future research and treatments in the field of gene therapy.

References:

1. Demirci, S., Uchida, N. & Tisdale, J. F. Gene therapy for sickle cell disease: An update. Cytotherapy 20, 899–910 (2018) 2. Niess, H. et al. Treatment of advanced gastrointestinal tumors with genetically modified autologous mesenchymal stromal cells (TREAT-ME1): Study protocol of a phase I/II clinical trial. BMC Cancer 15, 1–13 (2015). 3. Fan, XL., Zhang, Y., Li, X. et al. Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cell. Mol. Life Sci. 77, 2771–2794 (2020). https://doi.org/10.1007/s00018-020-03454-6 4. Petersdorf EW. Role of major histocompatibility complex variation in graft-versus-host disease after hematopoietic cell transplantation. F1000Res. 2017 May 3;6:617. doi: 10.12688/f1000research.10990.1. PMID: 28529723; PMCID: PMC5419254. 5. Houghton, B. C. & Booth, C. Gene Therapy for Primary Immunodeficiency. HemaSphere (2021) doi:10.1097/HS9.0000000000000509. 6. U.S National Library of Medicine. ClinicalTrials.gov. Accessed October 21, 2022. https://clinicaltrials.gov/ 7. Uchibori, R., Tsukahara, T., Ohmine, K. & Ozawa, K. Cancer gene therapy using mesenchymal stem cells. Int. J. Hematol. 99, 377–382 (2014). 8. Liang, Y. et al. The caspase-8 shRNA-modified mesenchymal stem cells improve the function of infarcted heart. Mol. Cell. Biochem. 397, 7–16 (2014). 9. Lien, C. Y., Ho, K. C. Y., Lee, O. K., Blunn, G. W. & Su, Y. Restoration of bone mass and strength in glucocorticoid-treated mice by systemic transplantation of CXCR4 and Cbfa-1 Co-Expressing Mesenchymal Stem Cells. J. Bone Miner. Res. 24, 837–848 (2009). 10. Internal data on file.