Immunity Boosters: Stem Cells vs. Immune Cells

When we think of the term "immunity", we think of feeling invincible against common ailments, easily recovering back from illnesses, or being less likely to catch a cold. But what exactly does immunity mean from a scientific point of view?

The immune system has three major functions: immune defense, immune surveillance, and internal environment stability. Immune defense revolves around combating infections and thwarting pathogens, while immune surveillance monitors and eliminates aberrant cells, including tumors and aging cells. Internal environment stability mainly involves the body's tolerance and regulation of its own immune response, maintaining the stability of the internal environment.

In short: If you want to improve your immunity, you essentially need to improve the function of your immune system. There are several studies showing how MSCs and NK/NKT therapy can improve immunity, so which one should we choose?

NK/NKT Cells: Guardians of Immunity

Natural Killer (NK) cells have long been recognized as formidable defenders of the immune system, but their lesser-known counterparts, Natural Killer T (NKT) cells, also play crucial roles in immune surveillance and response. Together, NK and NKT cells form a dynamic duo, regulating immune function and eliminating abnormal cells with precision.

The Function of NK Cells

NK cells are like the body's security guards, patrolling to keep us safe from harmful cells. They have special weapons, like lytic granules filled with molecules that can destroy stressed cells. Additionally, they have other tools called tumor necrosis factors, which can trigger harmful cells to self-destruct when they bind to certain receptors.

But NK cells do more than just attack bad cells. They also help regulate the immune system by balancing between signals that say "attack" and "stop." Certain receptors on their surface recognize specific molecules on healthy cells and tell the NK cells not to attack. However, if these molecules are missing or reduced on unhealthy cells, it's like removing the "stop" signal, so the NK cells know to attack.

On the other hand, there are receptors that directly tell NK cells to attack. When these receptors get activated, NK cells spring into action, ready to destroy any threats. They can even team up with antibodies to target and destroy harmful cells more effectively.

The Role of NKT Cells

While NK cells are like the first line of defense in the immune system, NKT cells bring an extra layer of protection. NKT cells are special because they have traits of both NK cells and T cells, which are important for fighting infections.

NKT cells can recognize specific molecules called glycolipid antigens, which are presented by certain cells in the body. When they detect these antigens, NKT cells spring into action and start producing cytokines, which are like messengers that help coordinate the immune response. This allows NKT cells to regulate both the immediate response and the long-term defense of the immune system, making them essential players in keeping us healthy.

Therapeutic Potential of NK and NKT Cell Therapies

The potential for using NK and NKT cells to boost the immune system is significant. There are different methods we can use, like giving the body extra cytokines to activate NK cells, or using NK cells from donors without needing a perfect match. We can also use CAR-NK therapy to target specific threats, although it can be expensive and have side effects.

Another approach is to use special antibodies that target harmful cells and activate NK cells to destroy them. Sometimes, we combine these antibodies with NK cells to make them even more effective at killing harmful cells.

It's also important to understand how NK and NKT cells work in the body after they've been activated. We know that NK cells don't last very long once they're activated, so we need to plan our treatments carefully to make sure they're effective. This knowledge helps us develop better ways to use these cells to fight diseases like viral infections.

Conclusion

NK and NKT cells are the superheroes in our immune system, working together to keep us healthy. While NK cells are great at fighting off bad cells directly, NKT cells have a special ability to fine-tune our immune responses.

By understanding how these cells work, we can develop new ways to boost our immune system and treat diseases. From cutting-edge therapies to targeted treatments, the future looks bright for improving our immunity.

Using NK and NKT therapies, we’re closer to the sweet spot where our bodies can fight off threats more effectively.

Repeated infusions of stem cells can delay the onset of diabetes and improve beta cell function and quality

Type 1 diabetes (T1D) is an autoimmune disease characterized by the progressive and irreversible loss of insulin-producing beta cells. Once diagnosed, T1D patients require lifelong exogenous insulin injections. Although intensive insulin therapy can improve glucose homeostasis, it cannot replace the function performed by the pancreatic islets, nor can it suppress the continued destruction of remaining beta cells by the autoimmune system. Therefore, preserving residual β-cell function and smoothing blood sugar fluctuations to reduce the incidence of chronic diabetic complications [1,2] , blocking autoimmune attacks, retaining or even restoring endogenous β-cell function have been long-sought solutions for T1D.

In an open- in Stem Cell Research & Therapy , researchers compared MSCs intervention with standard insulin in patients with type 1 diabetes admitted from 2013 to 2019. The effect of treatment . ( Registration number: ChiCTR2100045434 )

All participants had obvious symptoms of hyperglycemia at the time of onset, and 62.3% of the participants were complicated by diabetic ketosis or diabetic ketoacidosis (DKA). Participants were 8 to 55 years old at enrollment, required insulin injections since diagnosis of T1D, and had fasting C-peptide levels ≥100 pmol/L. Cardiopulmonary insufficiency, failure of one or more organs, HIV or viral hepatitis positivity, pregnancy, and underlying hematological, rheumatic, psychiatric, or malignant diseases were excluded.

Prior to the launch of clinical trials, the research team's studies in T1D animal models have obtained substantial evidence that transplantation of MSCs can delay the onset of T1D, reverse post-onset hyperglycemia, and improve β-cell function and quality [8,9,10 , 11,12] . MSCs mainly accumulated in pancreatic tissue 28 days after systemic infusion in non-obese diabetic (NOD) mice. MSC infusion significantly reduced islet inflammation, at least in part, by modulating the balance between pro- and anti-inflammatory and effector and regulatory T cells .

According to the research team's previous data, the effect of MSCs on maintaining beta cell function and regulating inflammation was dose-dependent in diabetic NOD mice, and multiple doses of MSCs prolonged their presence in pancreatic tissue and showed longer effect [9] . Furthermore, in a pilot trial of MSC transplantation for T1D, C-peptide levels trended downward after three months in recipients who received a single dose of MSCs (data not shown ) . Therefore, the research team decided to modify the mesenchymal stem cell-based immunomodulatory therapy and increase the course to repeat transplants three months apart. The aim was to evaluate the safety and efficacy of repeated allogeneic UC-MSCs in the treatment of T1D subjects.

At the end of 1-year follow-up, 11 subjects in the MSC treatment group maintained clinical remission ( 11/27, 40.7% ), while the clinical remission rate in the control group was significantly reduced ( 3/26, 11.5%, p = 0.041 ) . The HbA1c level in the MSC treatment group decreased significantly and reached the lowest level ( 6.6±0.8% ) at 3 months , but gradually increased to 6.9±1.1% and 7.3±1.3% at 6 and 12 months, respectively. The mean daily insulin dose requirements of MSC-treated individuals were relatively stable during follow-up.

Changes in HbA1c and exogenous insulin requirements during 1-year follow-up

The results of the study showed that both the control group and the MSC treatment group experienced clinical remission, but the subjects who received MSC treatment were four times more likely to achieve clinical remission than those who received regular insulin (OR=4.38, p= 0.044 ) . In addition, intravenous infusion of MSCs is safe, and the research team increased the course of repeated infusions of mesenchymal stem cells. Three recipients developed mild fever but recovered within 24 hours. This post-infusion febrile reaction has been reported in clinical trials for other diseases [21] , no serious adverse events were observed, and it was well tolerated by both adolescent and adult recipients.

Overall, this trial is the first to demonstrate that repeated intravenous infusion of allogeneic UC-MSCs is feasible and safe in individuals with T1D. Furthermore, it provides evidence that compared with standard treatment alone, the clinical response rate in the MSC treatment group was 40.7%, which was 2.5 times higher than that in the control group, and that this cell therapy may be beneficial in maintaining endogenous beta cell function .