Humans, in general, lack substantial regenerative capabilities, as compared to many non-human species, such as amphibians and certain fish. These organisms can repair, regenerate, and remodel substantial portions of many structures in their body and even in one of the least regenerative structures in the body such as their brain. This is even after critical life-threatening trauma.
Cell-based therapy has emerged as a promising approach to this problem. It enables the fabrication of functional tissues or organs that can further be used for reparative procedures in patients. However, this approach requires a donor tissue, and also extensive cell expansion before being used for implantation in therapy. Moreover, isolated tissue-derived primary cells are often heterogeneous and difficult to standardize. Thus, obtaining a reliable and reproducible cell source has been one of the challenging elements of cell-based approaches.
This has motivated the development of a new strategy that eliminates the ex vivo cell manipulation before implantation. Additionally this approach will also decrease the time, effort and resources required to generate a tissue/organ substitute.
Recent progress in regenerative medicine has adopted the concept of utilizing endogenous cells for in situ tissue regeneration. The principle of in situ tissue regeneration is to utilize the body’s own biologic resources and its reparative capability by using target specific bioactive molecules to recruit host stem or tissue specific progenitor cells to the site of injury. This novel approach would be to allow for a damaged tissue to be regenerated without the need for cell transplantation. These bioactive molecules would unlock the body’s own regenerative
capability. This would further induce the mobilization of tissue-specific host stem/ progenitor cells, drive proliferation and differentiation of these recruited cells into the targeted cell types, and regenerate functional tissues. These soluble factors get into the regulatory architecture of cells and support both reprogramming and early remodeling bio-activities of the new genome. Independently these factors do very little, but in the right synergy MOA arises – this is the stochastic way epimorphic regeneration / repair events naturally occur in tissues.
Reprogramming of cells in target tissues to a multi / pluripotent progenitor state
● A key to in situ tissue regeneration in the initial stage is proficient recruitment of host stem or progenitor cells. Adult stem cell populations in the body are generally too low in number to have a significant impact on accelerated tissue regeneration. Therefore, it is worthwhile to target these cells to be effectively mobilized into the peripheral blood system from bone marrow adipose tissue and other reservoirs.
● Bioactive molecules that induce engraftment of the mobilized host stem cells into desired tissues or organs for repair are considered as important cues for efficient in situ tissue regeneration.
● For differentiation into a desired tissue type, infiltrating cells are induced into tissue-specific cell lineages for functional tissue regeneration.This signals the endogenous stem cells for growth and differentiation.
● Bioactive molecules play an important role in guiding host cells to form a well-integrated functional structure. Most adult stem cells are quiescent and reside in a specialized microenvironment, called the ‘stem cell niche’. In response to regulatory signals that originate from tissue injury, these stem cells become activated and begin the repairing process. Bioactive molecules and biophysical cues enhance cell migration, proliferation,
and differentiation to produce a biofunctional host stem cell niche
● Modulate inflammatory response: peptides would help in innate immune response. This would lead to an appropriate level of activation of the regenerative side of the innate immune response (versus the adaptive immune response) to support morphogenesis
● They also mimic the regulatory characteristics of natural extracellular matrices (ECMs) and ECM-bound growth factors, both for therapeutic applications and basic biological studies.
● They activate present bioactive ligands and respond to cell-secreted signals to enable proteolytic remodeling. This sets an appropriate histolytica response for extracellular matrix remodeling in targeted tissues.
● These materials have already found application in differentiating stem cells into neurons, repairing bone and inducing angiogenesis.
● They also contain the necessary signals to recapitulate developmental processes in tissue-and organ-specific differentiation and morphogenesis.
Based on the last several decades of extensive in-vivo work using human embryonic cells, certain protein molecules have been identified to have a very high capacity to reprogram, regenerate, and repair any type of cell including neural, hepatic and renal etc.
● Peptides and m RNAs: these solutions contain highly active protein molecules and mRNAs. They have very high capacity to reprogram, regenerate and repair any cell type. They are highly effective on any cell types including neural, hepatic, renal, skin etc.
● General growth factors: these are purified mixture of growth factors which help in increasing stem cells in the general circulation, thus increasing the regenerative capacity of the complete body. They also increase survival of implanted/injected stem cells.
● Neural growth factor: these are specialized growth factors that help in homing of the stem cells in damaged /diseased neural tissues. It also helps stem cells differentiate into neurons, and stimulates the endogenous neural stem cells. For neurological indication, intralesional /intrathecal, and IM, the use of bioactive peptides and subcutaneous neural growth factors will be the best.
● For other indications, and IM applications for muscle and cartilage intraarticular,
bioactive peptides and subcutaneous administration of Genotrop are done.