The “Myth” of Homing: Why Do Cells Need A Delivery System?

Sep 12, 2022 | Homing

It is often thought that therapeutic cells make their way from the point of injection to the location they’re needed. However, this is highly debated, and based on a number of data points, homing works less often than you might believe. 

In this article, we will:

  • Define homing
  • Examine when homing works
  • Look at when homing doesn’t work
  • Explore why homing doesn’t work
  • Review the 7 factors that cause homing to not work
  • What you need to understand to make your cell therapy successful

What is Homing?

The fate of therapeutic cells injected into the bloodstream is a hotly contested area of research. In the early 2000s a concept called “Homing” was introduced1. The idea is that stem cells can be injected into the bloodstream and they “home” or find their way to the target site. How could this happen? Chemokines, a group of secreted proteins, send signals to the stem cells to attract them to certain areas2.

The homing of cells to target locations certainly happens naturally in the body and has been well documented. Examples include:

  • During embryogenesis, stem cells move as they differentiate so that intact organs and tissues will eventually be formed.
  • When a person gets a cut, nearby fibroblasts are signaled to enter the wound bed to form collagen to fill in the wound.

While the homing of cells can occur naturally in certain circumstances, the process is typically inadequate to overcome major injuries or illnesses. For example, if neurological stem cells homed to the area of a stroke and repaired the injured tissue, then there would be no long-term deficits following the incidence. Since millions of people suffer from the effects of a stroke, we know that the homing process is imperfect.

If native cells can’t home to a site of injury and regenerate new tissues in the body, then how can they be expected to do that when the cells are injected into the bloodstream as a therapy to treat disease?

The One Example of When Homing Works:

Hematopoietic Stem Cell Homing

To date, the majority of cell treatments have been applied systemically or locally, but without a method of delivery that will hold the cells in the target location. There is one example where the systemic delivery of cells via intravenous injections has been successful and that is when treating blood disorders.

Blood cancers such as multiple myeloma are often treated with stem cell transplants. After high doses of chemotherapy, the depleted bone marrow is rescued with bone marrow (hematopoietic) stem cells infused into the blood. These cells find their way to the bone marrow cavity where they take up long-term term residence 3. Homing is rapid in the human body with circulating hematopoietic stem cells crossing the vascular endothelium wall and entering the bone marrow cavity within hours3. The signaling that draws them to the bone marrow cavity first occurs with endothelial cells, which bind the stem cells, allowing them to migrate out of the bloodstream. As they move from the blood vessels to the bone marrow cavity, molecules like CXCL12, CXCR4 and CXCR7 are involved in maintaining the cells in the bone4.

The same is true for the treatment of blood cancers with immunotherapies.  The newest cancer treatment using genetically modified CAR-T cells can be infused into the blood because they are targeting leukemia and lymphoma cells that also reside in the blood. 

When Home Doesn’t Work:

Homing of Non-Hematopoietic Stem Cells

Evaluation of the present literature illustrates the challenges with systemic infusion of cells when targeting specific locations in the body. A review of the literature indicates that, when infused through the bloodstream, most cells are found in low numbers at the target area5. Areas of research that have been interested in therapeutic stem cell homing are focused on heart disease, liver disease and cancer. 

Heart disease

The concept of stem cells repairing the heart after heart attacks or other myocardial diseases has been a strong area of research. In a study of people with recent heart attacks, labeled bone marrow-derived stem cells were injected IV or directly into the heart via a coronary artery6. About an hour later, only 1-2% of the cells were detected in the region of the heart attack when infused into the coronary artery. With IV infusion, no cells could be detected in the area. In fact, the vast majority of cells were found trapped in the liver and spleen.

 

 

 

Read the rest of the article and learn more about:

  • Explore why homing doesn’t work
  • Review the 7 factors that cause homing to not work
  • What you need to understand to make your cell therapy successful

Download the full Homing article here:

Resources

1. Y. Saito, Y. Kametani, K. Hozumi, N. Mochida, K. Ando, M. Ito, T. Nomura, Y. Tokuda, H. Makuuchi, T. Tamjima, S. Habu, The in vivo development of human T cells from CD34+ cells in the murine thymic environment, Int Immuno 14(10) (2002) 1113-1124.

2. J. Foeng, I. Comerford, S. McColl, Harnessing the chemokine system to home CAR-T cells to solid tumors, Cell Rep Med 3(3) (2022) 100543.

3. T. Lapidot, A. Dar, O. Kollet, How do stem cells find their way home?, Blood 106(6) (2005) 1901-1910.

4. J. Liesveld, N. Sharma, O. Aljitawi, Stem cell homing: from physiology to therapeutics, Stem Cells 38(10) (2020) 1241-1253.

5. S. Kang, I. Shin, M. Ko, J. Jo, J. Ra, Journey of mesenchymal stem cells for homing: strategies to enhance efficacy and safety of stem cell therapy, Stem Cells Int 2012(342968) (2012) 11.

6. M. Hoffman, K. Wollert, G. Meyer, A. Menke, L. Arseniev, B. Hertenstein, A. Ganser, W. Knapp, H. Drexler, Monitoring of bone marrow cell homing into the infarcted human myocardium, Circulation 111(17) (2005) 2198-2202.

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