Blood-Derived Stem Cell Banking: A Present Option vs. Potential Future Induced Pluripotent Stem Cell Therapies

Normal aging results in a marked decline in immune functions, often referred to as immune senescence.

Some of these undesirable degenerative changes are:
– Decreased production of new immune cells
– Impaired function of the existing immune cells
– Increase of inflammation (also known as inflammaging)
– Reduced response to vaccines
– Accumulation of senescent stem cells and immune cells
– Increased rates of hematological malignancies (leukemia, lymphoma, myeloma) and solid cancers

Scientists today are developing methods to prevent or partially reverse age-related immune deficiencies and
mutations. This is incredible news!

In the meantime, proven technology is available now that can help preserve one’s immune system in its current younger state so that it is available when a stem cell transplant is needed.

This article describes how and why some people today are banking their own hematopoietic stem and progenitor stem cells (HSPCs) for future immune rescue.

Bone marrow is where hematopoietic stem and progenitor stem cells (HSPCs) are located, and they form blood and immune cells which are released into circulation.

When someone is stricken with a blood cancer like certain leukemias, treatment may involve ablating the patient’s bone marrow with aggressive chemotherapy and replacing the lost marrow with a stem cell (HSPC) transplant from a donor.
A stem cell (HSPC) transplant enables formation of new bone marrow that produces life-sustaining red blood cells, platelets, and immune cells.

While attempts are made to find a closely matched allogeneic donor (from a relative or an unrelated person), a potential lethal complication is graft-versus-host disease. This occurs when the transplanted stem cells (HSPCs) provoke an autoimmune attack against the body of the blood cancer patient.

In many cases, the leukemia patient achieves long term survival, but the patient may suffer an agonizing death from relentless and severe autoimmune attacks, i.e., graft-versus-host disease.

What if instead of finding a closely matched stem cell (HSPC) donor (even a 10/10 HLA donor is not a perfect match), the cancer patient had access to his or her own (autologous) younger stem cells (HSPCs) for transplant?
When autologous stem cells (HSPCs) are available for transplant, the risk of graft-versus-host disease plummets and treatment outcomes are improved.

Blood cancers like leukemias, lymphomas, and multiple myeloma are technically referred to as “hematologic malignancies”. The lifetime risk of contracting a hematologic malignancy is about 1 in 60, with some groups at higher risk such as those previously treated with chemotherapy drugs, radiation, and exposure to certain chemicals.

Hematopoietic Stem and Progenitor Cells (HSPCs)

The most important cells in the immune system are Hematopoietic Stem and Progenitor Cells (HSPCs) which are normally present in the bone marrow.

All other immune cells (B cells, T cells, macrophages, natural killer cells, etc.) are derived from these HSPCs.

HSPCs will divide and differentiate into all of these different immune cell types as well as red blood cells and platelets.

The technology that is available for preserving these cells is called immune cell or stem cell (HSPC) banking.

How Stem Cell (HSPC) Banking is Done

A person is first injected with a stem cell mobilization cytokine called G-CSF (granulocyte-colony stimulating factor) which temporarily increases stem cell (HSPC) numbers and releases these stem cells into the blood stream from the bone marrow.

This G-CSF has been used safely for decades to rescue bone marrow in cancer patients treated with aggressive chemotherapy that destroys vital bone marrow cells.

These mobilized (HSPC) stem cells are then collected from the blood and cryopreserved, i.e. frozen with a biological anti-freeze like chemical called DMSO to mitigate freezing damage.

If someone develops a hematological malignancy or other cancer that requires stem cell (HSPC) damaging chemotherapy, their cryopreserved stem cells (HSPCs) can be reinfused to form healthy new bone marrow, with very low risk of graft-versus-host disease.

Even more intriguing is that as someone ages, their stem cells (HSPCs) will be maintained and not undergo senescence or aging, and their cryopreserved stem cells can be injected back into them at a future time to restore their immune function. Immune dysfunction is associated with a host of degenerative illnesses including blood cancers.

Now let’s explore some of the technologies that could be around the corner for rejuvenating the immune system, assuming that all the challenges can be overcome.

Making New Young Hematopoietic Stem Cells (HSCs)

A new publication from researchers at the Murdoch Children’s Research Institute (MCRI) in Australia describes a method for taking normal human cells such as skin cells, and then turning them into HSCs[1].

Such HSCs could be used as a “perfect match” in bone marrow transplants to treat hematological disorders. The researchers state:

“The differentiation of human pluripotent stem cells (PS cells) into repopulating hematopoietic stem cells (HSCs) could provide novel therapeutic options for a range of hematopoietic disorders. For example, HSCs derived from patient induced PS cells (iPS cells) could circumvent the donor–host mismatch that leads to graft-versus-host-disease, a major source of morbidity and mortality in recipients of imperfectly matched allogenic transplants.”

Previously, researchers knew how to take human cells and turn them into induced pluripotent stem cells (iPSCs).

This is accomplished by exposing normal somatic (body) cells to a set of specific transcription factors which turn cellular reprogramming genes on and off. The transcription factors used are often Oct4, Sox2, Klf4, and c-Myc (OSKM). These are also referred to as “Yamanaka factors” after Dr. Shinya Yamanaka’s Nobel Prize-winning research findings[2].

In the MCRI study, they were then able to differentiate these iPSCs into HSCs which could then be used specifically for repopulating the immune system.

The researchers accomplished this by growing the cells in culture and sequentially guiding the cells through key developmental stages by exposing the cells to specific growth factors (VEGF, SCF, IGF2, etc.) at particular times.

They demonstrated that these new human cells (HSCs) were functional by transplanting them into immunodeficient mice which would not immunologically reject the transplant.

The cells were then able to engraft and repopulate all the bone marrow cell types of the immune system. Regarding potential applications, the authors mainly focused on treating hematological disorders and using the cells for disease modelling.

However, the same technique could potentially be used for rejuvenating the immune system. During the process of producing iPSCs, cells are made young again as the telomeres are lengthened and the DNA methylation clock is reset to a younger state[3].

Shortcomings of Making New Hematopoietic Stem Cells

This research holds great promise, but the techniques will need to be optimized and go through regulatory approval processes and clinical trials before these therapies are available for human patients.

In the Australian study, they found that the cells were able to engraft at levels comparable to established sources like (HSPCs) from cord blood[1]. Cord blood engraftment, however, is generally lower than peripheral blood (HSPCs) engraftment. They found that the frequency of engraftment with their iPS cell-derived HSCs (iHSCs) was 20-fold lower than the frequency obtained with normal mobilized peripheral blood[1].

Some of the methods used for producing iPSCs can also introduce genetic mutations and chromosomal
abnormalities[4,5]. This occurs because producing iPSCs requires expression of reprogramming factors, and introducing the genes for these factors into cells is often accomplished by viruses that insert the genetic material into the genome.

These insertions can occur between normal genes, disrupting normal genetic control and can lead to cancer.

Some of the reprogramming factors used to generate iPSCs such as c-Myc and Klf4, are also oncogenes[6]. This could pose a risk of cancer development in patients. iPSC cells, which are undifferentiated cells, can also be prone to forming teratomas[7].

The efficiency of reprogramming somatic cells into iPSCs is relatively low, and the resulting iPSCs can be heterogeneous. This variability can affect the consistency and reliability of iPSC-based therapies[8,9].

Although iPSCs can be derived from a patient’s own cells, there is still a risk of immune rejection[10–13]. This can occur due to incomplete reprogramming or the aberrant expression of genes during the reprogramming process. The immunogenicity of iPSCs is an active area of research.

While iPSCs bypass the ethical issues associated with embryonic stem cells, there are still ethical and regulatory issues regarding their use, especially in terms of genetic manipulation and long-term safety[4,14].

The production and maintenance of iPSCs are currently expensive and technically demanding. Scaling up the production for clinical use remains a significant challenge[15–17].

In addition to these challenges, ensuring that iPSCs fully differentiate into the desired cell type is crucial for their therapeutic use. Incomplete or incorrect differentiation can lead to the formation of unwanted cell types, reducing the efficacy and safety of the treatment[17].

While iPSCs offer exciting possibilities for medical advancements, addressing the current limitations is essential for their safe and effective clinical application.

Partial Cell Reprogramming

The method of partial reprogramming provides another avenue for rejuvenating the immune system. Partial reprogramming involves expressing many of the same reprogramming transcription factors that are expressed when making iPSCs, factors such as Oct4, Sox2, and Klf4 (OSK), for short periods of time to avoid full reprogramming to an iPSC state[3]. The c-Myc transcription factor is often excluded due to cancer risks.

Partial reprogramming has been shown to rejuvenate cells to a younger state by resetting the epigenetic DNA methylation clock to a younger state[3].

Current evidence, however, suggests that partial reprogramming does not substantially reset another hallmark of aging, the shortening of telomeres, because the enzyme telomerase which lengthens telomeres is not expressed at high levels until later stages of reprogramming[3,18,19]. The inability to lengthen telomeres could lead to cellular senescence later on.

There is significant interest and funding for partial reprogramming at the moment with well-funded companies such as Altos Labs, Calico Labs, Retro Biosciences, Turn Biotechnologies, LifeExtension, and others investigating the approach[20].

Although partial reprogramming appears promising, there are still technical and regulatory challenges to be overcome before such methods are used widely in patients.

In the Meantime. . . Bank Stem Cells (HSPCs) While They are Functional and Young

The therapeutic potential of iPSCs and techniques such as partial reprogramming appear promising, but we don’t know when or if these therapies will overcome all of the current challenges, successfully pass clinical trial regulations, and be widely used in patients.

In the meantime, you can use a technology that is available today, stem cell (HSPC) banking. This process involves collecting stem cells (HSPCs) from your blood and freezing them to preserve them for your later use.

You are your own perfect immunological match so immune rejection is of little concern.

Where is stem cell (HSPC) banking available?

The most common place for people to go for stem cell (HSPC) collection is hospitals, which may charge very high prices.

Since 2003, the Stem Cell Cryobank/SFBMSCTI/Maharaj Institute of Immune Regenerative medicine has had a Personalized/Private Blood Stem Cell (HSPC) and Immune Cell Banking Program which includes pre-harvest stem cell (HSPC) mobilization and peri-harvest including collection, processing, cryopreservation, and storage of individual’s cells for their own use later in life. The Stem Cell Cryobank/SFBMSCTI/Maharaj Institute of Immune Regenerative Medicine is AABB accredited and FDA registered for collection, processing, cryopreservation, and storage for adult blood HSPCs and newborn cord blood HSPCs processing, cryopreservation, and storage.

These cells (HSPCs) can be used for a bone marrow transplant for blood diseases such as leukemia, bone marrow disorders, and cancer. These cells can also be used for the same basic function to overcome the decreased function of stem cells (HSPCs) as well as the associated immune senescence and immune dysfunction that comes with the aging process.

These stem cells (HSPCs) are safe because they are the individual’s own cells with little risk of rejection or cancer. They are unmanipulated and the harvesting procedure can yield the high numbers of stem cells (HSPCs) needed for a complete stem cell (HSPC) transplant without the need for expansion in the lab.

This personalized private banking program for storing heathy stem cells (HSPCs) avoids the potential pitfalls of the use of manipulated cells such as HSCs from iPSCs. Alternatively, one could also choose to enhance their younger banked stem cells with future rejuvenation technologies once these methods have been optimized and proven safe.

If you are interested in banking your stem cells (HSPCs) through our program, please contact the Maharaj Institute of Immune Regenerative Medicine at our email info@bmscti.org or website https://maharajinstitute.com.

References
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2 Malik N, Rao MS. A Review of the Methods for Human iPSC Derivation. 2013:23–33.

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4 Gorecka J, Kostiuk V, Fereydooni A, et al. The potential and limitations of induced pluripotent stem cells to achieve wound healing. Stem Cell Res Ther. 2019;10:87. doi: 10.1186/s13287-019-1185-1

5 Lowden O. Advantages and disadvantages of induced pluripotent stem cells. https://blog.bccresearch.com/advantages-and-disadvantages-of-induced-pluripotent-stem-cells (accessed 7 September 2024)

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