How would you define the regenerative potential of a tissue/organ?

Dear stem cell biologists and bioinformaticians: I’ve got a pretty serious question for you. How would you define and quantify the native (endogeneous, in-built) regenerative potential of a tissue/organ or more generally of a specially localized functional cell population in the human body? In the literature the term “regenerative potential” of a tissue is often used concerning the response to damage and repair due to the contribution of the tissue-specific resident stem cell niche or from the circulation, but I haven’t found any strict and quantitative concept and definition yet. If you do please inform me. A working operational definition (update: of a regenerative potential of a tissue/organ) designed to model a conceptual definition could be the basic building block of a whole body regeneration model, which is needed for any attempt to launch systemic regenerative medicine.

So here is my initial offer:

Let us assume that we calculated the following cell numbers of a tissue/organ with some method (stereology, fluorescence activated cell sorter, theorethical calculation based on other measurements and data):

– number of differentiated functional cells

– number of tissue, organ and lineage specific endogenous stem cells

– number of tissue, organ specific progenitor (or transit amplifying cells TACs) cells.

Based on the estimated proportion of stem cell/differentiated cells or TACs/differentiated cells in a defined tissue or organ I’d like to introduce the tissue and organ specific theoretical and practical Regenerative Potential.

I define the Theorethical Regenerative Potential of a tissue or organ as follows: the ratio of quiscent self-renewing stem cells in a stem cell niche/differentiated cells in a tissue or organ. (Or we can use all cells= differentiated+stem+TACs as a denominator.)

Practical Regenerative Potential: the ratio of dividing progenitor cells which give rise to functioning differentiated cells/differentiated cells in a tissue or organ. (Or we can use all cells= differentiated+stem+TACs as a denominator.)

For example: the number of skeletal muscle cells in an adult human being are estimated: 2.50×10(8) or 250 million and the number of satellite cells which are considered as skeletal muscle stem cells is 1.25×10(7) or 12.5 million so the Theorethical Regeneration Potential of human skeletal muscle is 12.5 million/250 million=0.05
Of course it is not advisable to extrapolate from this data to other tissues, because the syncytial and somehow supracellular skeletal muscle is not a typical tissue. And we have to take into consideration the bone-marrow derived or myogenic cell contribution from the circulation.

The other restriction: the significance of this type of Regenerative Potential is dependent of the rate of cellular turnover of organs and tissues, which is rather heterogeneous.

3 thoughts on “How would you define the regenerative potential of a tissue/organ?

  1. One problem with your definition is that it doesn’t take into account how healthy the stem cells are. The same ratio of cells would have less regenerative capacity in an older person (due to both intrinsic and extrinsic factors).

  2. That’s a really good question Atilla. One of the challenges I see with a whole body regeneration model though is that the answer may be different based on the organ or system you evaluate due to the varied repair and regenerative pathways that each has. Some systems and organs may simply have decreased regenerative capabilities due to a lack of external signalling (e.g. endochrine decline, signalling for stem cell replacement), some may simply be due to an accumlation of damage and changes within cells for which the causes could be many and multivariate (DNA repair mechanisms,varied gene expression, ROS, shortening telomeres, accumulated junk, etc) that all individually or collectively somehow interfere with what appears to be a healthy self-sustaining process of self repair in younger versions of the organism. Would it make more sense to look for an operational definition by organ or system?

    Personally I’m still a fairly junior researcher in the area of aging so I think one of the other big guns of biogerontology could give you a better answer. I look forward to their responses as any progress in this area would be a would have invaluable medical applications.

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